ArticlePDF Available

Abstract

Molluscs have proven to be invaluable models for basic neuroscience research, yielding fundamental insights into a range of biological processes involved in action potential generation, synaptic transmission, learning, memory, and, more recently, nociceptive biology. Evidence suggests that nociceptive processes in primary nociceptors are highly conserved across diverse taxa, making molluscs attractive models for biomedical studies of mechanisms that may contribute to pain in humans but also exposing them to procedures that might produce painlike sensations. We review the physiology of nociceptors and behavioral responses to noxious stimulation in several molluscan taxa, and discuss the possibility that nociception may result in painlike states in at least some molluscs that possess more complex nervous systems. Few studies have directly addressed possible emotionlike concomitants of nociceptive responses in molluscs. Because the definition of pain includes a subjective component that may be impossible to gauge in animals quite different from humans, firm conclusions about the possible existence of pain in molluscs may be unattainable. Evolutionary divergence and differences in lifestyle, physiology, and neuroanatomy suggest that painlike experiences in molluscs, if they exist, should differ from those in mammals. But reports indicate that some molluscs exhibit motivational states and cognitive capabilities that may be consistent with a capacity for states with functional parallels to pain. We therefore recommend that investigators attempt to minimize the potential for nociceptor activation and painlike sensations in experimental invertebrates by reducing the number of animals subjected to stressful manipulations and by administering appropriate anesthetic agents whenever practicable, welfare practices similar to those for vertebrate subjects.
Volume 52, Number 2 2011 185
Abstract
Molluscs have proven to be invaluable models for basic
neuroscience research, yielding fundamental insights into a
range of biological processes involved in action potential
generation, synaptic transmission, learning, memory, and,
more recently, nociceptive biology. Evidence suggests that
nociceptive processes in primary nociceptors are highly con-
served across diverse taxa, making molluscs attractive mod-
els for biomedical studies of mechanisms that may contribute
to pain in humans but also exposing them to procedures that
might produce painlike sensations. We review the physiol-
ogy of nociceptors and behavioral responses to noxious
stimulation in several molluscan taxa, and discuss the pos-
sibility that nociception may result in painlike states in at
least some molluscs that possess more complex nervous sys-
tems. Few studies have directly addressed possible emotion-
like concomitants of nociceptive responses in molluscs.
Because the defi nition of pain includes a subjective compo-
nent that may be impossible to gauge in animals quite dif-
ferent from humans, firm conclusions about the possible
existence of pain in molluscs may be unattainable. Evolu-
tionary divergence and differences in lifestyle, physiology,
and neuroanatomy suggest that painlike experiences in mol-
luscs, if they exist, should differ from those in mammals. But
reports indicate that some molluscs exhibit motivational
states and cognitive capabilities that may be consistent with
a capacity for states with functional parallels to pain. We
therefore recommend that investigators attempt to minimize
the potential for nociceptor activation and painlike sensa-
tions in experimental invertebrates by reducing the number
of animals subjected to stressful manipulations and by
administering appropriate anesthetic agents whenever
practicable, welfare practices similar to those for vertebrate
subjects.
Key Words: Aplysia; cephalopod; ethics; invertebrate;
mollusc; nociception; pain; sensitization
Nociceptive Biology and Evolution
Nearly all animals that have been studied display
marked behavioral responses to stimuli that cause
tissue damage—the ability to sense and respond to
noxious stimuli is an almost universal trait (Kavaliers 1988;
Smith and Lewin 2009; Sneddon 2004; Walters 1994). Noci-
ception, defi ned as the detection of stimuli that are injurious
or would be if sustained or repeated, has clear adaptive ad-
vantages because it triggers withdrawal and escape during
injury or in the face of impending injury.
Nociception and Nociceptive Sensitization
The fi rst stage of nociception occurs with the activation of
nociceptors, primary sensory neurons preferentially sensitive to
noxious stimuli or to stimuli that would become noxious
if prolonged (Sherrington 1906). Nociceptors were fi rst
demonstrated in Chordata by Burgess and Perl (1967), in
Annelida by Nicholls and Baylor (1968), in Mollusca by
Walters and colleagues (1983a), in Nematoda by Kaplan and
Horvitz (1993), and in Arthropoda by Tracey and colleagues
(2003). Preliminary studies indicate that nociception in these
phyla involves many conserved sensory transduction processes
(Smith and Lewin 2009; Tobin and Bargmann 2004; Tracey
et al. 2003), although differences have also been found. It is
not yet known whether specialized nociceptors also occur in
other phyla, although this seems likely.
Many nociceptors exhibit a property rare among primary
sensory neurons: enhanced sensitivity produced by intense
stimulation of the sensory neuron’s peripheral terminals
(Campbell and Meyer 1983; Gold and Gebhart 2010; Hucho
and Levine 2007; Illich and Walters 1997; Light et al. 1992).
Enhancement of the sensitivity of a nociceptor, nociceptive
network, or behavioral response after noxious stimulation is
called nociceptive sensitization (Walters 1994; Woolf and
Walters 1991).
Nociceptive sensitization can be measured directly at the
neuronal and behavioral levels and has been investigated exten-
sively in mammals because it is thought to represent concrete,
quantifi able effects that in humans are related to increased
pain sensitivity. As defi ned by the International Association
for the Study of Pain (IASP; Merskey and Bogduk 1994),
increased pain sensitivity occurs in the form of hyperalgesia
(greater pain in response to a normally painful stimulus) and
allodynia (pain evoked by a stimulus that is not normally
painful).
Robyn J. Crook and Edgar T. Walters
Robyn J. Crook, PhD, is a postdoctoral fellow and Edgar T. Walters, PhD, a
professor in the Department of Integrative Biology and Pharmacology at the
University of Texas Medical School at Houston.
Address correspondence and reprint requests to Dr. Robyn J. Crook,
Department of Integrative Biology and Pharmacology, University of Texas
Medical School at Houston, 6431 Fannin Street, Houston, TX 77030 or
email Robyn.Crook@uth.tmc.edu.
Nociceptive Behavior and Physiology of Molluscs: Animal Welfare Implications
186 ILAR Journal
In a few molluscs and other invertebrates, mechanisms of
nociceptive sensitization have been investigated intensively
in hopes of discovering fundamental processes that contrib-
ute to hyperalgesia and allodynia in humans and other ani-
mals. Indeed, behavioral and neurophysiological alterations
in nociceptors during nociceptive sensitization appear
remarkably similar in snails and rats (Walters 1994, 2008;
Woolf and Walters 1991), and these alterations involve many
intra- and extracellular biological signaling pathways that
are highly conserved (Walters and Moroz 2009).
Interpreting Nociceptive Differences
across Phyla
There are numerous differences between the neuronal sys-
tems that mediate nociceptive sensitization in molluscs and
in mammals (as well as presumably enhanced pain in the
latter). At the axonal level, molluscs and other invertebrates
lack myelination, so conduction of information from one
part of the nervous system to another is usually much slower
than in vertebrates. At the synaptic level, an evolutionarily
recent expansion of the synaptic proteome in vertebrates
may underlie unique cognitive capabilities of this group (Ryan
and Grant 2009) and in principle also contribute to a poten-
tially unique capacity of vertebrates to experience pain.
Furthermore, at the neuroanatomical and, presumably,
neural network levels, little homology exists across any of
the phyla, which diverged before most of the evolution of
neuroanatomical structures in contemporary animals (Farris
2008). Thus noxious information in vertebrates is relayed
from primary nociceptors via neurons in the dorsal horn of
the spinal cord to brain structures including the thalamus and
the somatosensory, insular, and anterior cingulate cortices
(Peyron et al. 2000), but homologues to these brain struc-
tures do not exist in invertebrates. The fact that these areas
are not present in the invertebrate central nervous system
(CNS1) does not prove that invertebrates cannot feel pain;
independently derived neural structures might, in principle,
have evolved the capacity to mediate the same functions. For
example, some invertebrates (many cephalopods and some
insects) can process highly complex visual information even
though they lack a structure homologous to the mammalian
visual cortex. While it is plausible that the more elaborate
neural structures of mammals confer a capacity for the expe-
rience of pain, analogous processing in other phyla might
mediate painlike experiences using neural structures unrelated
to and quite different from those in the mammalian brain.
Similarity across phyla of nociceptive behavior, mecha-
nisms of nociception, and nociceptive sensitization implies
either deep homology of underlying mechanisms or conver-
gence arising from similar selection pressures among diverse
and distantly related taxa. Either of these possibilities may
permit insights into mechanisms important for pain and its
alleviation in vertebrates from studies of animals with far
1Abbreviation that appears 3x throughout this article: CNS, central nervous
system
simpler nervous systems. Invertebrates thus present two consid-
erable advantages: (1) research on a complex process in a sim-
pler system often permits a clearer picture of what is really
important, and (2) the study of states bearing similarities to pain
or unpleasantness in an animal that appears to have less capac-
ity to interpret and “feel” such sensations is more palatable to
scientists, to the public, and to animal welfare committees.
The presence in invertebrates of some nociceptive mech-
anisms that are homologous and/or convergent with those
important for pain in humans presents a question of ethics: If
scientists are willing to appeal to evolutionary conservatism
to support the use of “lower” animals to study physiological
building blocks that in humans contribute to pain and suffer-
ing (assuming that the information revealed will translate
to humans and other “higher” vertebrates), is it acceptable to
ignore possible implications of evolutionary conservation
that similar processing of nociceptive information by higher
and lower animals might in each case produce suffering? Are
there reasons to think that experimental unpleasantness is
less keenly felt by a snail or fl y than by a mouse, monkey, or
human, and if so where should one draw the line when con-
ducting experiments that might cause suffering?
Nociception Versus Pain
Humans tend to experience nociception and pain as a single
phenomenon, but for the study of animals it is important to
draw a distinction between sensory activation and emotional
perception (see Braithwaite 2010 for an excellent discussion
of the separable nature of the two processes).
Defi ning Nociception and Pain
Nociception is a capacity to react to tissue damage or im-
pending damage with activation of sensory pathways, with
or without conscious sensation. Activity in nociceptive sen-
sory pathways usually results in refl exive behavioral responses
and may or may not result in other responses. Refl exive with-
drawal responses tend to be mediated by very simple senso-
rimotor circuits optimized for speed and reliability and can
occur without input from higher processing centers, although
more complex escape and avoidance behaviors involve more
complex neural circuits (Chase 2002; Walters 1994). Even in
humans the initial refl exive response to a noxious stimulus is
sometimes faster than can be consciously perceived, and
nociceptors can sometimes be activated without conscious
sensation (Adriaensen et al. 1980). Invertebrates that lack
appropriate processing centers may be capable of only this
rapid, unconscious processing.
The defi nition of pain widely accepted by scientifi c in-
vestigators is “an unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or de-
scribed in terms of such damage” (Merskey and Bogduk 1994).
The emotional component required by this defi nition of pain
makes its identifi cation in other species, and especially in
species quite different from humans, extremely diffi cult, if
Volume 52, Number 2 2011 187
not impossible. This is because emotion is usually defi ned in
terms of conscious experience (e.g., Izard 2009), and while
evidence of consciousness in some animals is available,
proof of consciousness is not (e.g., Allen 2004).
It is therefore important to distinguish between nocicep-
tion as detection of a noxious stimulus (which can be recog-
nized scientifi cally by unambiguous behavioral and neural
responses), and pain as the unpleasant feeling associated
with that stimulus (and inferred by behavioral and neural re-
sponses of uncertain relation to consciousness).
Moreover, the emotional response during pain may be
linked to cognition, “knowing” in some sense that the sensa-
tion is negative and involves a threat to the body. Whereas
nociception leading to a nociceptive response can be medi-
ated by the simplest of neural circuits (in principle just a
single nociceptor connected to an effector system—e.g., a
muscle), pain requires neural circuitry that incorporates
additional functions, some of which might entail highly
complex processing by very large numbers of neurons.
Identifying Nociception and Pain in Animals
In invertebrates, like mammals, responses to noxious stimu-
lation can be complex. Indeed, immediate defensive responses
to injury or noxious stimulation are followed by a longer-
term phase (sometimes lasting weeks or months) where dam-
aged regions are hypersensitive (e.g., Walters 1987b) and some
invertebrates remember associations of the noxious event with
its context (e.g., Colwill et al. 1988; Walters et al. 1981).
To date, long-term nociceptive sensitization in inverte-
brates has been explained by long-term alterations of primary
sensory neurons (especially nociceptors) (e.g., Montarolo et al.
1986; Scholz and Byrne 1987; Walters 1987a) and motor
neurons (e.g., Cleary et al. 1998; Glanzman 2008; Weragoda
et al. 2004); there is little evidence for electrical activity or
alterations in other types of neurons that outlast a noxious
stimulus for more than tens of minutes (see Cleary et al.
1998; Marinesco et al. 2004). Interneurons and modulatory
neurons have received far less experimental attention be-
cause they are much more diffi cult to identify and sample
with the intracellular recording methods used for neurophys-
iological experiments on invertebrates. Truly systematic
investigations of the distribution and duration of enhanced
activity (possible neural correlates of pain) across an entire
nervous system will benefi t from the development of func-
tional imaging methods for invertebrates (for a start, see Frost
et al. 2007; Zecevic et al. 2003) equivalent to those used to
examine patterns of activity in the mammalian brain after
noxious stimulation (e.g., Peyron et al. 2000; Tracey and
Bushnell 2009).
Several considerations suggest that pain may be absent
in at least some invertebrates. Capacities for processing all
types of information, including that involved in pain or pain-
like phenomena, increase with the size and complexity of a
nervous system, and mammals with the most complex brains
have, thus far, shown the most evidence for a capacity for
humanlike pain, although this might refl ect a far greater ex-
perimental effort directed at vertebrates rather than genuine
differences in the invertebrate pain experience.
Nociceptive refl exes and nociceptive plasticity can occur
without conscious, emotional experience because these re-
sponses are expressed not only in the simplest animals but
also in reduced preparations, such as spinalized animals
(Clarke and Harris 2001; Egger 1978) and snail ganglia
(Walters et al. 1983b). Similarly, in human patients nocicep-
tive refl exes can occur without conscious awareness below a
level of complete spinal transection (Finnerup and Jensen
2004).
But conservation or convergence of physiological and
molecular mechanisms of nociception and nociceptive sensi-
tization across distant phyla does not necessarily imply that
higher-order phenomena (such as pain) that can be supported
by these mechanisms are equivalent. Even if the critical
mechanisms turn out not to be equivalent, it is not possible to
be certain that an animal does not feel pain, and thus the ethi-
cal questions remain (Allen 2004).
How can researchers balance the opportunities some
invertebrates offer for discovering mechanisms that, for
example, may alleviate chronic pain or slow dementia in
humans, with the possibility that the invertebrate subjects
might suffer? This is a fundamental problem for all of bio-
medical research, but has received very little consideration
in invertebrate studies. We refer readers to other articles in
this issue (Elwood 2011; Mather 2011) dealing with ethical
and philosophical considerations of invertebrate use.
Nociception and Painlike Phenomena
in Mollusca
Molluscs have provided invaluable models for neuroscience,
yielding a wealth of basic information applicable to humans
and other vertebrates. A consideration of their nociceptive
behavior and physiology will inform choices about their op-
timal use for biomedical research and improve the welfare of
molluscs used in the laboratory.
Mollusca is a highly diverse and successful metazoan
phylum with over 100,000 species (Ponder and Lindberg 2008)
distributed among terrestrial, aquatic, and marine environments
and divided into seven classes: Aplacophora, Polyplaco-
phora, Monoplacophora, Scaphopoda, Bivalvia, Gastropoda,
and Cephalopoda. Along with great diversity in body plan,
lifestyle, and ecology, Mollusca encompasses enormous
intraphylum variation in sensory organs and neuroanatomy
(Bullock and Horridge 1965). Because the capacity for sens-
ing and integrating information about the environment and
an individual’s own body is probably important for the abil-
ity to feel pain or experience distress, this large variation in
neural and sensory complexity suggests that welfare con-
cerns may differ among groups.
The primary model species considered here are from the
gastropod and cephalopod clades; members of the other
classes are discussed briefl y.
188 ILAR Journal
Aplacophora, Polyplacophora,
Monoplacophora, and Scaphopoda
The classes less commonly used in neurobiological research
tend to be the primitive, sedentary, or deepwater-dwelling
groups.
Aplacophora contains small wormlike molluscs that bur-
row into the substrate (Salvini-Plawen 1981) and have paired
ventral and dorsal nerve cords running along the body as
well as paired cerebral and buccal ganglia in the head. Visual
and vestibular organs are absent but putative mechanosensory
neurons innervate the oral surface (Shigeno et al. 2007).
Little is known about their behavior and nothing about the
physiology of sensory neurons.
Polyplacophora contains the chitons, generally intertidal
marine animals with multiple platelike shells covering the
dorsal surface. They have a simple nervous system without
pronounced cephalization. There are rows of primitive pho-
toreceptors along the dorsal surface and mechanosensory
organs around the mouth.
Monoplacophora is also an exclusively marine taxon of
limpetlike, conically shelled molluscs. Scaphopoda have a
single, tusklike shell through which water is pumped while
the animal remains mostly buried in the substrate. In both of
these groups the neural networks are simple and apparently
unspecialized and the ganglia are small. The simplicity of
their nervous systems and their behavior suggest that the
possibility of these animals experiencing painlike responses
to tissue insult is remote.
Bivalvia
The Bivalvia (e.g., oysters, clams, mussels, and scallops) are
abundant in both marine and freshwater environments. Their
nervous system includes two pairs of nerve cords and three
pairs of ganglia (Brusca and Brusca 2003). There is no obvi-
ous cephalization and the nervous system appears quite sim-
ple. A population of mechanosensory neurons is activated
during the foot withdrawal refl ex in a razor clam, but it is not
known if these are nociceptors (Olivo 1970).
Clams and scallops have simple eyes and chemosensory
organs located along the periphery of the mantle and they
initiate escape swimming if a threat is detected, thus some
integration of information and basic decision making occurs.
Escape swimming in scallops is driven by a motor pattern
generator in the cerebral ganglion and usually occurs after
chemosensory detection or contact with a starfi sh predator
that would normally precede tissue destruction (Wilkins
1981), suggesting that nociception may be involved. How-
ever, to our knowledge there are no published descriptions of
behavioral or neurophysiological responses to tissue injury
in bivalves.
Although a number of studies have claimed that en-
dogenous opioids (e.g., Stefano and Salzet 1999) and opioid
receptors (e.g., Cadet and Stefano 1999) are expressed in
the mussel Mytilus edilus, particularly in immunocytes,
neither genes for proopiomelanocortin (POMC) nor opi-
oid receptors are found in Drosophila melanogaster or
Caenorhabditus elegans, and their reported existence in
other invertebrates, including molluscs, is controversial (Dores
et al. 2002; Li et al. 1996).
Gastropoda
This class includes terrestrial, freshwater, and marine spe-
cies (e.g., snails, slugs, limpets, whelks, and many others).
Typically the shell and body are coiled, although in some
taxa (e.g., terrestrial slugs, sea hares, nudibranchs) the shell
is absent.
Gastropods have more diverse and specialized sensory
organs than the groups above and are typically motile and
active foragers. Along with increased range of habitats and
associated morphologies, their behavioral range is greater
and this is refl ected in increased neural complexity. The basic
molluscan nervous system is present (Bullock and Horridge
1965) but is expanded in terms of both the number of cells
and their specialization. Many gastropods have giant neu-
ronal somata, which have been used to advantage for neu-
ronal analyses of behavioral mechanisms (Chase 2002;
Kandel 1976) and perhaps most prominently for investiga-
tions of learning and memory mechanisms (Kandel 2001).
Gastropods have also provided the largest number of studies
of nociceptive behavior and sensitization in invertebrates, in
part because noxious mechanical and electrical stimuli have
been used in many learning and memory studies. Some of
these studies have used pulmonate (air-breathing) snails but
most have used opisthobranch (rear-positioned gills) snails.
We know of no studies of nociceptive behavior or physiology
in the remaining group of gastropods—the prosobranchs.
Pulmonates
Pulmonates descended from gastropod molluscs that moved
from the sea to terrestrial and freshwater habitats. The most
extensively studied pulmonate is Helix (several different
species on different continents), which is prey to many gen-
eralist predators such as birds and frogs. Thus the well-
developed defensive and aversive behaviors elicited by noxious
sensory input during failed predation attempts in this genus
should be subject to continuing selection.
When presented with a potentially threatening tactile
stimulus to soft tissue, Helix, like other pulmonates, with-
draws refl exively, a behavior mediated by simple neural cir-
cuitry including sensory neurons that appear to be nociceptors
(Balaban 2002; Ierusalimsky and Balaban 2007). Noxious
stimulation can sensitize this behavior. Repeated electric
shocks to the foot (which probably activate nociceptors) re-
sult in a reduced response threshold to an innocuous me-
chanical stimulus that persists several days after the shocks,
and this long-term behavioral sensitization is associated with
several alterations in the circuit that mediates the withdrawal
response (Balaban 1983, 1993; Prescott and Chase 1999).
Volume 52, Number 2 2011 189
Other pulmonates used to investigate responses to nox-
ious stimuli include Lymnaea stagnalis (Sakharov and Rozsa
1989) and Megalobulimus abbreviatus (Kalil-Gaspar et al.
2007). The latter study is of interest because it provided
pharmacological evidence for nociceptive actions of an ion
channel highly expressed in mammalian nociceptors (the tran-
sient receptor potential cation channel subfamily V member
1, or TRPV1, the capsaicin receptor).
As explained above, the ability to perceive noxious in-
formation as emotionally unpleasant is a delineating point
between simple nociception and pain. Helix, with a brain
containing only about 20,000 neurons in 11 ganglia, might
be presumed to be incapable of higher-order processing nec-
essary for emotional responses. Interestingly, however, some
evidence suggests an emotionlike reaction in Helix.
Experiments using electrodes implanted into two differ-
ent ganglia allowed animals to “self-stimulate” either of the
two neural regions by pressing a bar (Balaban 1993; Balaban
and Chase 1991). Results from this experiment suggested
that different CNS regions of snails have some rudimentary
“emotional coloration”: snails self-stimulated more fre-
quently when the electrodes were placed in the mesocerebral
region of the cerebral ganglion (containing some neurons in-
volved in sexual behavior) and less frequently when they
were placed in the rostral portion of the parietal ganglion, in
an area where electrical stimulation of putative nociceptive
sensory neurons underlying refl exive withdrawal behavior
was likely (Balaban 2002). But relatively little is known
about the anatomical organization and actual functions of
most neurons in either of these ganglionic regions. A lack of
follow-up reports of snail self-stimulation raises questions
about the robustness of this fi nding.
An apparent ability to remember and choose to avoid a
negative stimulus would suggest that a snail can selectively
modify its behavior on the basis of aversive experience in
ways similar to mammals. This would not show that Helix
can experience pain but it would suggest that fundamental
components of painlike information processing in vertebrates
might be present in a rudimentary fashion in some molluscs.
Opisthobranchs
The marine opisthobranch Aplysia californica is the leading
invertebrate model system for analyzing cellular bases of
behavioral and neural plasticity in many contexts (Kandel
1976, 2001). Aplysia has nine central ganglia containing
only about 10,000 neurons (Cash and Carew 1989), of which
several hundred have been identifi ed by soma size and loca-
tion, electrophysiological properties, synaptic connections,
and behavioral effects. Aplysia and many other molluscs
also have numerous neuronal cell bodies in peripheral nerve
nets (Bullock and Horridge 1965; Moroz 2006).
Most studies of learning and memory mechanisms in
Aplysia have used known mechanosensory neurons. Initial
studies used these neurons in the abdominal ganglion that
innervate the siphon (Byrne et al. 1974), but later studies
used homologous sensory neurons in each pleural ganglion
that innervate most of the rest of the body surface (Walters et al.
1983a, 2004). Moreover, both sets of neurons function as
nociceptors (Illich and Walters 1997; Walters et al. 1983a)
and thus their rich plasticity is highly relevant to nociceptive
functions. Both sets of nociceptors display prominent sensi-
tizing effects, associated with short- and long-term sensitiza-
tion of defensive behavior (gill and siphon withdrawal, tail
withdrawal, head withdrawal) after noxious stimulation.
These effects include enhancement of synaptic transmission
(reviewed by Kandel 2001; Walters 1994) and hyperexcit-
ability of the nociceptor expressed in its peripheral terminals
(especially near a site of injury), neuronal cell body, axons,
and near its presynaptic terminals (Billy and Walters 1989;
Gasull et al. 2005; Reyes and Walters 2010; Weragoda et al.
2004). Such alterations are similar to those described in
studies of nociceptive sensitization in rodents and humans,
suggesting that some mechanisms that promote pain in ver-
tebrates are also present in molluscs and, most likely, in
other invertebrate taxa as well (Walters and Moroz 2009).
Interesting similarities also exist in the behavioral re-
sponses of Aplysia and mammals to noxious stimulation.
Aplysia displays the nearly ubiquitous pattern of immediate
withdrawal refl exes, rapid escape, and prolonged recupera-
tive behaviors exhibited across all major phyla (reviewed by
Kavaliers 1988; Walters 1994; see also Babcock et al. 2009;
Walters et al. 2001).
In addition, Aplysia responds with a motivational state
resembling conditioned fear to previously neutral chemosen-
sory stimuli associated with noxious electric shock (Walters
et al. 1981). For example, after pairing with shock, the smell
of shrimp evoked a state that was not obvious unless com-
bined with other stimuli—indeed, when only the shrimp
extract was presented, the animal exhibited a response remi-
niscent of the freezing exhibited by rats to a conditioned fear
stimulus (Walters et al. 1981). When tested in combination
with weak tactile stimulation, the shrimp extract greatly facili-
tated head and siphon withdrawal responses, defensive ink-
ing, and escape locomotion. Moreover, when delivered to a
feeding animal, the conditioned smell inhibited the feeding.
These extensive and motivationally consistent associa-
tive alterations (see also Colwill et al. 1988) suggest that
memory of a noxious event in snails can be linked to a fear-
like motivational state that can dramatically alter the animal’s
response to other biologically signifi cant stimuli. Unfortunately,
almost nothing is known about the neuroanatomical loci and
specifi c neurons involved in this “higher-order” processing
of nociceptive information in opisthobranch ganglia.
Nociceptive sensitization has also been reported in the
marine nudibranch Tritonia diomedea (Frost et al. 1998),
and associatively conditioned avoidance behavior after nox-
ious conditioning stimulation has been investigated in the
notaspid Pleurobranchaea californica (Jing and Gillette 2003;
Mpitsos and Davis 1973). Both of these species offer many
advantages for cellular analyses, but they are diffi cult to ob-
tain commercially and have been investigated much less
extensively than has Aplysia.
190 ILAR Journal
In most animals, including Aplysia, nociceptive path-
ways show a period of inhibition after strong noxious stimu-
lation as the animal engages in escape and active defense
(Mackey et al. 1987; Walters 1994). Opioids contribute sub-
stantially to nociceptive inhibition in vertebrates but, despite
indirect evidence for opioid signaling—such as pharmaco-
logical actions of opioids (e.g., met-enkephalin) and opioid
antagonists (e.g., naloxone) in molluscs (Kavaliers 1988;
Leung et al. 1986)—molecular evidence does not yet pro-
vide fi rm support for true opioid signaling in invertebrates
(Dores et al. 2002). Moreover, application of enkephalins
fails to produce inhibitory effects on the gill withdrawal re-
ex (Cooper et al. 1989) or known nociceptors (Brezina et al.
1987) in Aplysia. Instead another peptide, FMRFamide, may
be a major transmitter that produces immediate and long-
term suppressive effects on nociceptor excitability, synaptic
transmission, and defensive refl exes in Aplysia (Belardetti
et al. 1987; Mackey et al. 1987; Montarolo et al. 1988).
Cephalopoda
Cephalopoda is an exclusively marine class that comprises
squid, cuttlefi sh, octopus, and nautilus. The cephalopod shell
is chambered and external in nautilus, internal in cuttlefi sh,
and reduced or absent in squid and octopuses. Cephalopods
are the most neurologically complex invertebrates, with cen-
tralized brains divided into specialized lobes capable of pro-
cessing and integrating complex visual, chemical, and tactile
sensory inputs. The octopus CNS has around 500 million
cells (Young 1963), vastly more than that of gastropods. The
octopus also has an enormous peripheral nervous system,
separate from the CNS (Rowell 1966; Young 1963). Indeed,
the number of neuronal cell bodies in the arms of the octopus
is close to that of the central brain.
Cephalopods show complex behavior and are excellent
learners, with reports of sensitization, habituation, associative
learning, spatial learning, and even (although controversial)
observational learning (see reviews by Hanlon and Messenger
1998; Hochner et al. 2006). Despite the extensive literature
on cephalopod behavior, there have been no systematic be-
havioral or physiological investigations into nociception and
nociceptive plasticity.
Cephalopods are also less commonly used for studies of
neurophysiology due to the complex neuroanatomy of the
cephalopod CNS, the small size of the neuronal cell bodies,
and the lack of overshooting action potentials or large synaptic
potentials that can be recorded from the cell bodies (Hochner
et al. 2006). Nothing is known about where nociceptive in-
formation is processed in the cephalopod brain. Evidence for
nociception in cephalopods is therefore exclusively behavioral.
In various learning paradigms electric shock to the arms
of an octopus has been used effectively as a negative rein-
forcement (Boycott and Young 1955; Darmaillacq et al. 2004;
Shomrat et al. 2008; Young 1961), indicating that the animal
nds this stimulation aversive, but nociceptors have not yet
been described in any cephalopod. Octopuses are capable of
regenerating damaged or amputated arms, but there are no
published studies of behavioral adaptations to damaged or
healing tissue.
Although electric shock elicits defensive responses, an
intriguing anecdote from Jacques Cousteau (1973, 23-24) de-
scribing an octopus’ behavior during exposure to damag-
ing heat suggests the absence of a response to intense thermal
stimulation:
One day at Octopus City, in the Bay of Alicaster, Dumas
dived with an underwater rocket and began waving it in
front of an octopus’ house. Nothing happened. The ani-
mal reacted not at all. He did not try to hide, or to escape.
Dumas then turned the beam directly onto the octopus,
which did not even draw [sic] its arms. The game was
called off, however, when Dumas saw that it was becom-
ing cruel. The octopus showed signs of having been
burned. But even then it had not tried to escape from it.…
This surprising insensitivity to fi re has been confi rmed by
Guy Hilpatric, one of the pioneers of diving, who told us
that he has seen an octopus, which had been brought onto
shore, cross through a fi re to get back into the water.
Although it is potentially valuable for an animal (particularly
an intertidal species) to sense when environmental tempera-
tures are approaching dangerous levels, selection pressure
for nociceptors tuned to extreme heat is unlikely in most
aquatic animals. It would certainly be interesting to examine
this question in marine invertebrates adapted for life around
hydrothermal vents where extreme heat exposure may be a
hazard. An interesting question following from Cousteau’s
anecdote is whether the burned octopus would eventually
sense and respond to signals released by the damaged fl esh
or to infl ammatory mediators released during repair of the
tissue, as occurs in mammals.
Apart from the nautilus, which retains its external shell,
cephalopods have traded the protection of the molluscan
shell for an increase in locomotive effi ciency and speed.
Their soft bodies, almost completely unprotected, should be
subject to occasional survivable injuries during failed preda-
tion attempts, food contests, and mating competitions. It thus
seems probable that nociceptors exist in cephalopods. We
have begun our own investigations into this possibility by
examining behavioral responses of the squid (Loligo pealei)
to peripheral, sublethal injury to an arm (R. Crook, T. Lewis,
R. Hanlon, and E.T. Walters, unpublished observations).
Sensitization of defensive responses to tactile and visual
stimuli occurs and persists for at least 48 hours after injury,
suggesting that basic behavioral responses to injury in ce-
phalopods may be similar to those in gastropods and verte-
brates, but further study is needed.
Notwithstanding the lack of evidence for pain perception
in cephalopods, in the United Kingdom octopus are covered
by the same welfare act that governs procedures on verte-
brates (UK Animals [Scientifi c Procedures] Act 1986)2 and
2Available online (www.legislation.gov.uk/ukpga/1986/14/contents), accessed
on April 4, 2011.
Volume 52, Number 2 2011 191
in Canada and Europe an approved welfare protocol is re-
quired for the use of cephalopod species in research (CCAC
1993; EU directive 86/609/EEC, updated September 20103).
Cephalopods have far more complex brains and behav-
iors than any other invertebrate and are capable of impres-
sive cognitive tasks (see Hochner et al. 2006, for review).
For example, both the brainy octopus (Boal et al. 2000) and
“primitive” nautilus (Crook et al. 2009) are capable of verte-
bratelike spatial learning. Given these sophisticated cogni-
tive abilities, an important question is whether nociceptive
responses in cephalopods are accompanied by affective and
cognitive processing functionally similar to some of the pro-
cessing that is important for pain states in mammals.
Anesthesia in Molluscs
Until the early 1970s physiological and biochemical studies
of molluscs dispensed with any anesthetics. This practice re-
ected the widespread assumption that invertebrates cannot
feel pain, a view that is still common (and used to condone,
for example, the preparation of living cephalopods, snails,
and lobsters for human meals by methods that would cause
intense, prolonged stimulation of nociceptors if applied to
mammals).
Several studies of the mechanisms of action of widely
used mammalian anesthetics exploited the experimental
advantages of the giant axon of the squid and the giant cell
bodies in gastropod molluscs such as Aplysia (e.g., Frazier
et al. 1975; Winlow et al. 1992). But these anesthetics were
not used by researchers during their dissections, in part be-
cause many of the mammalian anesthetics and analgesics,
including opioids (Cooper et al. 1989), were not very effec-
tive in molluscs (although there were interesting exceptions,
including volatile general anesthetics that potently open po-
tassium channels that hyperpolarize and reduce excitability
in Aplysia nociceptors; Winegar et al. 1996; Winegar and
Yost 1998). The widespread use of anesthesia during dissec-
tion of Aplysia began when investigators interested in learn-
ing and memory realized that dissection without anesthesia
could cause sensitizing effects that would interfere with the
neuronal plasticity they were studying.
The anesthetic of choice for both gastropods (Pinsker
et al. 1973) and cephalopods (Messenger et al. 1985; Mooney
et al. 2010) is isotonic magnesium chloride solution, typi-
cally applied by injection for gastropods and immersion for
cephalopods. Magnesium ions provide an ideal anesthetic
(and muscle relaxant) because they are normally present at
relatively high concentrations (especially in marine mol-
luscs) and thus are relatively nontoxic, their effects are rap-
idly reversible, and the agent is both inexpensive and highly
effective (Walters 1987b). The effectiveness of magnesium
chloride in gastropods is a result of its inhibition of neu-
rotransmitter release at chemical synapses, its depressive ef-
fect on voltage-gated sodium channels, reducing membrane
3Available online (http://ec.europa.eu/environment/chemicals/lab_animals/
home_en.htm), accessed on April 4, 2011.
excitability (e.g., Liao and Walters 2002), and the fact that it
is used at high concentrations and injection volumes (>25%
of the animal volume) in combination with a balanced reduc-
tion of sodium ions (a reduction that by itself reduces excit-
ability). Effectiveness probably also depends on leakiness of
the primitive blood-ganglion or blood-nerve barriers of most
molluscs (Abbott 1987). Applied magnesium chloride does
not penetrate these barriers in vertebrates, precluding its use
as an anesthetic in mammals. Given that cephalopods also
have a highly effective blood-brain barrier (ibid.) and rela-
tively impermeable skin, the mechanisms underlying the
anesthesia that occurs during the animal’s immersion in iso-
tonic magnesium chloride are an interesting mystery.
We refer readers to Cooper (2011, in this issue) for fur-
ther discussion of analgesia and anesthesia in invertebrates.
Evolutionary Selection Pressures and
Painlike Phenomena in Molluscs
Insight into the extent to which nociception may lead to pain
in molluscs can come from considering possible selective
advantages of pain during evolution.
Nociception, like any prominent trait in animals, has
been selected and refi ned over millions of years by evolu-
tionary processes that act to enhance survival and reproduc-
tive success. The adaptive value of nociception is obvious
and probably universal: it permits rapid avoidance of a dam-
aging stimulus and escape from the context in which such
damage occurs. Escape may be from predators, aggressive
conspecifi cs, or threatening environmental features (e.g.,
rough surf).
The adaptive value of experiencing pain is more diffi cult
to identify, although clues are available from likely conse-
quences of nociceptive responses for survival under natural
conditions. A strong negative emotion motivates rapid avoid-
ance learning, decreasing the chances of reexposure to a nox-
ious stimulus. This interpretation raises the question of how
much neural processing power is required for emotional re-
sponses. Behaviorally expressed motivational states (defi ned
without reference to consciousness) mediated by the actions
of neuromodulators on relatively simple circuits in Aplysia
have been suggested to have functional similarities to emo-
tional states in mammals (Kupfermann 1979), and this is
consistent with properties of the conditioned fearlike state in
Aplysia described above. However, from a functional and
evolutionary point of view, there is no need for these states
to involve conscious experience by the animal.
In social animals, awareness and communication of in-
jury can be advantageous, allowing not only the behavioral
alterations that guard or rest an injured body part (at the ex-
pense of other behaviors such as foraging) but also the re-
cruitment of caregivers to help protect and provide for an
incapacitated individual during recovery. In nonsocial animals
(which may include all molluscs, as even those that ag-
gregate do so opportunistically for exploitation of a local
resource, not for social interactions), obvious behavioral
192 ILAR Journal
changes resulting from injury may be neutral or maladaptive
(attracting the attention of predators or aggressive conspe-
cifi cs). Thus it is unlikely that painlike states would have
evolved in molluscs to promote communication with poten-
tial caregivers.
Animals with high metabolic rates, such as squid, must
forage frequently to survive and thus cannot suppress active
behavior for very long during recuperation (when pain is of-
ten worst in mammals), so this common behavioral correlate
of pain would be maladaptive in such animals, although on-
going pain that promotes minor behavioral changes to protect
an injured appendage as a tradeoff against small reductions
in foraging success may be highly adaptive. Animals under
predation pressure (which includes almost all molluscs, and
particularly those lacking primary defenses such as a hard
shell or aposematic signals) probably derive minimal value
from sustained painful “feelings” if their expression renders
them more vulnerable to predators. Thus, while an acute re-
sponse to injury promoting escape and survival should be
strongly selected, and long-term increases in sensitivity to
potentially threatening stimuli are likely to be adaptive (Walters
1994), persistent painlike states that profoundly alter ongo-
ing behavior (e.g., decreasing foraging or mating activity)
may not be adaptive in molluscs.
Conclusions
All molluscs examined have shown a capacity for nocicep-
tion as demonstrated by behavioral responses and/or by
direct recording from nociceptors and other neurons. Noci-
ception and nociceptive sensitization at the level of primary
nociceptors make use of neuronal mechanisms that appear to
be highly conserved and widespread throughout the animal
kingdom.
But not all mechanisms related to nociceptive biology
are widely shared. For example, analgesiclike effects mediated
by true opioids and opioid receptors may be absent in inver-
tebrates (Dores et al. 2002), and vertebrates may possess
some synaptic mechanisms that are absent in invertebrates
(Ryan and Grant 2009). Moreover, the sharing of many basic
molecular building blocks does not imply sharing of higher-
order processes that depend on those building blocks. For
example, nearly all known brain functions in most phyla
depend on action potentials generated by the operation of
highly conserved sodium channels, but only a few species
have brains with the capacity to learn a spoken language or
do arithmetic—thus voltage-gated sodium channels are es-
sential for learning German or solving equations, but their
presence does not imply the capacity for profi ciency in Ger-
man or algebra. At some level this must also be true for the
capacity to experience pain.
Immediate and longer-term neuronal and behavioral re-
sponses (including nociceptive memory and simple associa-
tive learning) can be mediated entirely by a single small
ganglion, such as the abdominal ganglion in Aplysia, prov-
ing that these effects do not need complex neural structures
(e.g., Antonov et al. 2003; Illich and Walters 1997). Some
gastropods, which have simple nervous systems compared to
cephalopods, exhibit changes in state with apparent func-
tional similarities to emotional states, as illustrated by “con-
ditioned fear” and “self-stimulation” in Aplysia and Helix,
respectively (Balaban and Chase 1991; Walters et al. 1981).
Given the capabilities of relatively simple molluscan
nervous systems, and if a key to the experience of pain is the
size and complexity of the nervous system, one must seri-
ously consider the possibility that cephalopods can experi-
ence some form of pain. The most complex and behaviorally
sophisticated of molluscs, cephalopods have vastly more
complex central nervous systems, with up to 500 million
neurons, distinctive internal divisions of the brain, specialized
integrative regions where diverse sensory inputs are pro-
cessed (Boycott and Young 1955), and dense, specialized in-
nervation of the periphery (Hochner et al. 2006). If subjective
pain experience requires a minimal level of network com-
plexity and processing power, these animals’ brains might
approach that level.
Scientifi cally accepted defi nitions of pain and nocicep-
tion neatly distinguish these concepts (e.g., Merskey and
Bogduk 1994), but drawing a line between the two can be
diffi cult in practice. Furthermore, no experimental observation
of nonverbal animals (nonhumans) can demonstrate conclu-
sively whether a subject experiences conscious pain (Allen
2004). Suggestive evidence for painlike experiences in some
animals is available, and nociceptive responses measured at
the neural and behavioral levels in molluscs have provided
evidence that is both consistent and inconsistent with pain-
like states and functions. Unfortunately, inferences drawn
from the relatively small body of relevant data in molluscs
are limited and prone to anthropocentrism. Identifying signs
of pain becomes increasingly diffi cult as the behavior and
associated neural structures and physiology diverge from
familiar mammalian patterns of behavior, physiology, and
anatomy, making interpretation of responses in molluscs
particularly diffi cult.
In the laboratory, molluscs are often subjected to manip-
ulations that produce nociceptive responses, either as the aim
of an experiment or as a byproduct. Profound differences
between molluscs and mammals in the size, complexity, and
structure of their nervous systems, as well as their lifestyles
and evolutionary history, suggest that painlike phenomena, if
they exist in some molluscs, are likely to be quite different
from pain in mammals, although it does not follow that mol-
luscs are incapable of experiencing pain. Gastropod and
cephalopod molluscs have shown long-lasting behavioral
alterations induced by noxious experience, which probably
involve motivational states that can be used fl exibly to alter
defensive and appetitive responses. This suggests that some
molluscs may be capable not only of nociception and noci-
ceptive sensitization but also of neural states that have some
functional similarities to emotional states associated with
pain in humans.
While it seems improbable that any mollusc has a capac-
ity to feel pain equivalent to that evident in social mammals,
Volume 52, Number 2 2011 193
the existence of some similarities in nociceptive physiology
between molluscs and mammals, the paucity of systemic in-
vestigations into painlike behavior in molluscs, and the logi-
cal impossibility of disproving the occurrence of conscious
experience in other animals all suggest that it is appropriate
to treat molluscs as if they are susceptible to some form of
pain during experimental procedures.
In conclusion, we recommend that the design of experi-
ments using molluscs, particularly those with larger and more
complex ganglia or brains (especially cephalopods but also
gastropods), take into account the possibility of a capacity
for painlike experience in these animals. Effective anesthet-
ics (e.g., magnesium chloride) should be used during dissec-
tions and, to the extent possible, during any procedure that
produces tissue damage or possible stress. Investigators whose
experiments unavoidably produce noxious stimulation should
employ efforts similar to those required for vertebrate sub-
jects to reduce both the number of animals and the potential
for suffering to the minimum needed to test their hypotheses.
Balancing the benefi ts from knowledge gained in mol-
luscan experiments with the potential for infl icting pain and
distress in the experimental subjects should be an explicit
consideration in molluscan studies. (For related guidance to
IACUC members, we refer readers to Harvey-Clark 2011, in
this issue.)
Acknowledgments
Supported by NIH grant NS35979 (ETW) and a Marine Bio-
logical Laboratory Fellowship (RJC).
References
Abbott NJ. 1987. Neurobiology: Glia and the blood-brain barrier. Nature
325:195.
Adriaensen H, Gybels J, Handwerker HO, Van Hees J. 1980. Latencies of
chemically evoked discharges in human cutaneous nociceptors and of
the concurrent subjective sensations. Neurosci Lett 20:55-59.
Allen C. 2004. Animal pain. Nous 38:617-643.
Antonov I, Antonova I, Kandel ER, Hawkins RD. 2003. Activity-dependent
presynaptic facilitation and hebbian LTP are both required and interact
during classical conditioning in Aplysia. Neuron 37:135-147.
Babcock DT, Landry C, Galko MJ. 2009. Cytokine signaling mediates UV-
induced nociceptive sensitization in Drosophila larvae. Curr Biol 19:
799-806.
Balaban PM. 1983. Postsynaptic mechanism of withdrawal refl ex sensitiza-
tion in the snail. J Neurobiol 14:365-375.
Balaban P. 1993. Behavioral neurobiology of learning in terrestrial snails.
Prog Neurobiol 41:1-19.
Balaban PM. 2002. Cellular mechanisms of behavioral plasticity in terres-
trial snail. Neurosci Biobehav Rev 26:597-630.
Balaban PM, Chase R. 1991. Interrelationships of the emotionally positive
and negative regions of the brain of the edible snail. Neurosci Behav
Physiol 21:172-180.
Belardetti F, Kandel ER, Siegelbaum SA. 1987. Neuronal inhibition by the
peptide FMRFamide involves opening of S K+ channels. Nature 325:153-
156.
Billy AJ, Walters ET. 1989. Long-term expansion and sensitization of
mechanosensory receptive fi elds in Aplysia support an activity-depen-
dent model of whole-cell sensory plasticity. J Neurosci 9:1254-1262.
Boal JG, Dunham AW, Williams KT, Hanlon RT. 2000. Experimental evi-
dence for spatial learning on octopuses, Octopus bimaculoides. J Comp
Psychol 114:246-252.
Boycott BB, Young JZ. 1955. A memory system in Octopus vulgaris Lamarck.
Proc R Soc London B 143:449-480.
Braithwaite V. 2010. Do Fish Feel Pain? New York: Oxford University
Press.
Brezina V, Eckert R, Erxleben C. 1987. Modulation of potassium conduc-
tances by an endogenous neuropeptide in neurones of Aplysia califor-
nica. J Physiol 382:267-290.
Brusca RC, Brusca GJ. 2003. Invertebrates, 2nd ed. Sunderland MA: Sinauer
Associates.
Bullock TH, Horridge GA. 1965. Structure and Function in the Nervous
System of Invertebrates. San Francisco: W.H. Freeman.
Burgess PR, Perl ER. 1967. Myelinated afferent fi bres responding specifi -
cally to noxious stimulation of the skin. J Physiol 190:541-562.
Byrne J, Castellucci V, Kandel ER. 1974. Receptive fi elds and response
properties of mechanoreceptor neurons innervating siphon skin and
mantle shelf in Aplysia. J Neurophysiol 37:1041-1064.
Cadet P, Stefano GB. 1999. Mytilus edulis pedal ganglia express mu opiate
receptor transcripts exhibiting high sequence identity with human neu-
ronal mu1. Brain Res Mol Brain Res 74:242-246.
Campbell JN, Meyer RA. 1983. Sensitization of unmyelinated nociceptive
afferents in monkey varies with skin type. J Neurophysiol 49:98-110.
Cash D, Carew TJ. 1989. A quantitative analysis of the development of the
central nervous system in juvenile Aplysia californica. J Neurosci 20:
25-47.
CCAC [Canadian Council on Animal Care]. 1993. Guide to the Care and
Use of Experimental Animals, vol 1. Olfert ED, Cross BM, McWilliam
AA, eds. Ottawa: CCAC.
Chase R. 2002. Behavior and Its Neural Control in Gastropod Molluscs.
Oxford; New York: Oxford University Press.
Clarke RW, Harris J. 2001. The spatial organization of central sensitization
of hind limb fl exor refl exes in the decerebrated, spinalized rabbit. Eur
J Pain 5:175-185.
Cleary LJ, Lee WL, Byrne JH. 1998. Cellular correlates of long-term sensi-
tization in Aplysia. J Neurosci 18:5988-5998.
Colwill RM, Absher RA, Roberts ML. 1988. Context-US learning in Aply-
sia californica. J Neurosci 8:4434-4439.
Cooper JE. 2011. Anesthesia, analgesia, and euthanasia of invertebrates.
ILAR J 52:196-204.
Cooper BF, Krontiris-Litowitz JK, Walters ET. 1989. Humoral factors re-
leased during trauma of Aplysia body wall. II. Effects of possible me-
diators. J Comp Physiol B 159:225-235.
Cousteau JY. 1973. Octopus and Squid: The Soft Intelligence. New York:
Doubleday Press.
Crook RJ, Hanlon RT, Basil JA. 2009. Memory of visual and topographical
features suggests spatial learning in nautilus (Nautilus pompilius L.).
J Comp Psychol 123:264-274.
Darmaillacq AS, Dickel L, Chichery MP, Agin V, Chichery R. 2004. Rapid
taste aversion learning in adult cuttlefi sh, Sepia offi cinalis. Anim Behav
68:1291-1298.
Dores RM, Lecaude S, Bauer D, Danielson PB. 2002. Analyzing the evolu-
tion of the opioid/orphanin gene family. Mass Spectrom Rev 21:220-243.
Egger MD. 1978. Sensitization and habituation of dorsal horn cells in cats.
J Physiol 279:153-166.
Elwood RW. 2011. Pain and suffering in invertebrates? ILAR J 52:175-
184.
Farris SM. 2008. Evolutionary convergence of higher brain centers span-
ning the protostome-deuterostome boundary. Brain Behav Evol 72:106-
122.
Finnerup NB, Jensen TS. 2004. Spinal cord injury pain: Mechanisms and
treatment. Eur J Neurol 11:73-82.
Frazier DT, Murayama K, Abbott NJ, Narahashi T. 1975. Comparison of the
action of different barbiturates on squid axon membranes. Eur J Phar-
macol 32:102-107.
Frost WN, Brandon CL, Mongeluzi DL. 1998. Sensitization of the Tritonia
escape swim. Neurobiol Learn Mem 69:126-135.
194 ILAR Journal
Frost WN, Wang J, Brandon CJ. 2007. A stereo-compound hybrid micro-
scope for combined intracellular and optical recording of invertebrate
neural network activity. J Neurosci Methods 162:148-154.
Gasull X, Liao X, Dulin MF, Phelps C, Walters ET. 2005. Evidence that
long-term hyperexcitability of the sensory neuron soma induced by
nerve injury in Aplysia is adaptive. J Neurophysiol 94:2218-2230.
Glanzman DL. 2008. New tricks for an old slug: The critical role of post-
synaptic mechanisms in learning and memory in Aplysia. Prog Brain
Res 169C:277-292.
Gold MS, Gebhart GF. 2010. Nociceptor sensitization in pain pathogenesis.
Nat Med 16:1248-1257.
Hanlon RT, Messenger JB. 1998. Cephalopod Behaviour. Cambridge:
Cambridge University Press.
Harvey-Clark C. 2011. IACUC challenges in invertebrate research. ILAR
J 52:213-220.
Hochner B, Shomrat T, Fiorito G. 2006. The octopus: A model for a com-
parative analysis of the evolution of learning and memory mechanisms.
Biol Bull 210:308-317.
Hucho T, Levine JD. 2007. Signaling pathways in sensitization: Toward a
nociceptor cell biology. Neuron 55:365-376.
Ierusalimsky VN, Balaban PM. 2007. Primary sensory neurons containing
command neuron peptide constitute a morphologically distinct class of
sensory neurons in the terrestrial snail. Cell Tissue Res 330:169-177.
Illich PA, Walters ET. 1997. Mechanosensory neurons innervating Aplysia
siphon encode noxious stimuli and display nociceptive sensitization.
J Neurosci 17:459-469.
Izard CE. 2009. Emotion theory and research: Highlights, unanswered
questions, and emerging issues. Annu Rev Psychol 60:1-25.
Jing J, Gillette R. 2003. Directional avoidance turns encoded by single in-
terneurons and sustained by multifunctional serotonergic cells. J Neuro-
sci 23:3039-3051.
Kalil-Gaspar P, Marcuzzo S, Rigon P, Molina CG, Achaval M. 2007. Cap-
saicin-induced avoidance behavior in the terrestrial Gastropoda Mega-
lobulimus abbreviatus: Evidence for TRPV-1 signaling and opioid
modulation in response to chemical noxious stimuli. Comp Biochem
Physiol A Mol Integr Physiol 148:286-291.
Kandel ER. 1976. Cellular Basis of Behavior. San Francisco: W.H. Freeman.
Kandel ER. 2001. The molecular biology of memory storage: A dialogue
between genes and synapses. Science 294:1030-1038.
Kaplan JM, Horvitz HR. 1993. A dual mechanosensory and chemosensory
neuron in Caenorhabditis elegans. Proc Natl Acad Sci U S A 90:2227-
2231.
Kavaliers M. 1988. Evolutionary and comparative aspects of nociception.
Brain Res Bull 21:923-931.
Kupfermann I. 1979. Modulatory actions of neurotransmitters. Annu Rev
Neurosci 2:447-465.
Leung MK, Rozsa KS, Hall A, Kuruvilla S, Stefano GB, Carpenter DO.
1986. Enkephalin-like substance in aplysia nervous tissue and actions of
leu-enkephalin on single neurons. Life Sci 38:1529-1534.
Li X, Keith DEJ, Evans CJ. 1996. Mu opioid receptor-like sequences are
present throughout vertebrate evolution. J Mol Evol 43:179-184.
Light AR, Shults RC, Jones SL. 1992. The Initial Processing of Pain and Its
Descending Control: Spinal and Trigeminal Systems. Basel: S Karger.
Liao X, Walters ET. 2002. The use of elevated divalent cation solutions
to isolate monosynaptic components of sensorimotor connections in
Aplysia. J Neurosci Meth 120:45-54.
Mackey SL, Glanzman DL, Small SA, Dyke AM, Kandel ER, Hawkins RD.
1987. Tail shock produces inhibition as well as sensitization of the
siphon-withdrawal refl ex of Aplysia: Possible behavioral role for pre-
synaptic inhibition mediated by the peptide Phe-Met-Arg-Phe-NH2.
Proc Natl Acad Sci U S A 84:8730-8734.
Marinesco S, Kolkman KE, Carew TJ. 2004. Serotonergic modulation in
aplysia. I. Distributed serotonergic network persistently activated by
sensitizing stimuli. J Neurophysiol 92:2468-2486.
Mather J. 2011. Philosophical background of attitudes toward and treatment
of invertebrates. ILAR J 52:205-212.
Merskey H, Bogduk N. 1994. Part III: Pain Terms, A Current List with
Defi nitions and Notes on Usage. In: Classifi cation of Chronic Pain, 2nd
ed, IASP Task Force on Taxonomy. Merskey H, Bogduk N, eds. Seattle:
IASP Press. p 209-214.
Messenger JB, Nixon M, Ryan KP. 1985. Magnesium chloride as an anaes-
thetic for cephalopods. Comp Biochem Physiol C 82:203-205.
Montarolo PG, Goelet P, Castellucci VF, Morgan J, Kandel ER, Schacher S.
1986. A critical period for macromolecular synthesis in long-term het-
erosynaptic facilitation in Aplysia. Science 234:1249-1254.
Montarolo PG, Kandel ER, Schacher S. 1988. Long-term heterosynaptic
inhibition in Aplysia. Nature 333:171-174.
Mooney A, Lee W, Hanlon RT. 2010. Long duration anesthetization of
squid, Doryteuthis pealei. Mar Fr Behav Physiol 43:297-303.
Moroz LL. 2006. Localization of putative nitrergic neurons in peripheral
chemosensory areas and the central nervous system of Aplysia califor-
nica. J Comp Neurol 495:10-20.
Mpitsos GJ, Davis WJ. 1973. Learning: Classical and avoidance condition-
ing the mollusk Pleurobranchaea. Science 180:317-320.
Nicholls JG, Baylor DA. 1968. Specifi c modalities and receptive fi elds of
sensory neurons in CNS of the leech. J Neurophysiol 31:740-756.
Olivo RF. 1970. Mechanoreceptor function in the razor clam: Sensory
aspects of the foot withdrawal refl ex. Comp Biochem Physiol 35:
761-786.
Peyron R, Laurent B, Garcia-Larrea L. 2000. Functional imaging of brain
responses to pain: A review and meta-analysis. Neurophysiol Clin 30:263-
288.
Pinsker HM, Hening WA, Carew TJ, Kandel ER. 1973. Long-term sensiti-
zation of a defensive withdrawal refl ex in Aplysia. Science 182:1039-
1042.
Ponder WF, Lindberg DR. 2008. Phylogeny and Evolution of the Mollusca.
Berkeley and Los Angeles: University of California Press.
Prescott SA, Chase R. 1999. Sites of plasticity in the neural circuit mediat-
ing tentacle withdrawal in the snail Helix aspersa: Implications for be-
havioral change and learning kinetics. Learn Mem 6:363-380.
Reyes FD, Walters ET. 2010. Long-lasting synaptic potentiation induced by
depolarization under conditions that eliminate detectable Ca2+ signals.
J Neurophysiol 103:1283-1294.
Rowell CH. 1966. Activity of interneurones in the arm of Octopus in
response to tactile stimulation. J Exp Biol 44:589-605.
Ryan TJ, Grant SG. 2009. The origin and evolution of synapses. Nat Rev
Neurosci 10:701-712.
Sakharov DA, Rozsa KS. 1989. Defensive behaviour in the pond snail,
Lymnaea stagnalis: The whole body withdrawal associated with exsan-
guination. Acta Biol Hung 40:329-341.
Salvini-Plawen L. 1981. On the origin and evolution of the Mollusca. Att
Convegni Lincei 49:235-293.
Scholz KP, Byrne JH. 1987. Long-term sensitization in Aplysia: Biophysi-
cal correlates in tail sensory neurons. Science 235:685-687.
Sherrington CS. 1906. The Integrative Action of the Nervous System. New
Haven: Yale University Press.
Shigeno S, Sasaki T, Haszprunar G. 2007. Central nervous system of
Chaetoderma japonicum (Caudofoveata, Aplacophora): Implications
for diversifi ed ganglionic plans in early molluscan evolution. Biol Bull
213:122-134.
Shomrat T, Zarrella I, Fiorito G, Hochner B. 2008. The octopus vertical lobe
modulates short-term learning rate and uses LTP to acquire long-term
memory. Curr Biol 18:337-342.
Smith ES, Lewin GR. 2009. Nociceptors: A phylogenetic view. J Comp
Physiol A Neuroethol Sens Neural Behav Physiol 195:1089-1106.
Sneddon LU. 2004. Evolution of nociception in vertebrates: Comparative
analysis of lower vertebrates. Brain Res Brain Res Rev 46:123-130.
Stefano GB, Salzet M. 1999. Invertebrate opioid precursors: Evolutionary
conservation and the signifi cance of enzymatic processing. Int Rev
Cytol 187:261-286.
Tobin DM, Bargmann CI. 2004. Invertebrate nociception: Behaviors, neu-
rons and molecules. J Neurobiol 61:161-174.
Tracey I, Bushnell MC. 2009. How neuroimaging studies have challenged
us to rethink: Is chronic pain a disease? J Pain 10:1113-1120.
Tracey WDJ, Wilson RI, Laurent G, Benzer S. 2003. painless, a Drosophila
gene essential for nociception. Cell 113:261-273.
Volume 52, Number 2 2011 195
Walters ET. 1987a. Multiple sensory neuronal correlates of site-specifi c
sensitization in Aplysia. J Neurosci 7:408-417.
Walters ET. 1987b. Site-specifi c sensitization of defensive refl exes in Aply-
sia: A simple model of long-term hyperalgesia. J Neurosci 7:400-407.
Walters ET. 1994. Injury-related behavior and neuronal plasticity: An evo-
lutionary perspective on sensitization, hyperalgesia, and analgesia. Int
Rev Neurobiol 36:325-427.
Walters ET. 2008. Evolutionary aspects of pain. In: Basbaum A, Bushnell
CM, eds. Pain, vol 5. Burlington MA: Academic Press/Elsevier. p 175-
184.
Walters ET, Moroz LL. 2009. Molluscan memory of injury: Evolutionary
insights into chronic pain and neurological disorders. Brain Behav Evol
74:206-218.
Walters ET, Carew TJ, Kandel ER. 1981. Associative learning in aplysia:
Evidence for conditioned fear in an invertebrate. Science 211:504-506.
Walters ET, Byrne JH, Carew TJ, Kandel ER. 1983a. Mechanoafferent neu-
rons innervating tail of Aplysia. I. Response properties and synaptic
connections. J Neurophysiol 50:1522-1542.
Walters ET, Byrne JH, Carew TJ, Kandel ER. 1983b. Mechanoafferent neu-
rons innervating tail of Aplysia. II. Modulation by sensitizing stimula-
tion. J Neurophysiol 50:1543-1559.
Walters ET, Illich PA, Weeks JC, Lewin MR. 2001. Defensive responses of
larval Manduca sexta and their sensitization by noxious stimuli in the
laboratory and fi eld. J Exp Biol 204:457-469.
Walters ET, Bodnarova M, Billy AJ, Dulin MF, Diaz-Rios M, Miller MW,
Moroz LL. 2004. Somatotopic organization and functional properties of
mechanosensory neurons expressing sensorin-A mRNA in Aplysia cali-
fornica. J Comp Neurol 471:219-240.
Weragoda RM, Ferrer E, Walters ET. 2004. Memory-like alterations in
Aplysia axons after nerve injury or localized depolarization. J Neurosci
24:10393-10401.
Wilkins LA. 1981. Neurobiology of the scallop. I. Starfi sh-mediated escape
behaviours. Proc R Soc Lond B 211:341-372.
Winegar BD, Owen DF, Yost CS, Forsayeth JR, Mayeri E. 1996. Volatile
general anesthetics produce hyperpolarization of Aplysia neurons by
activation of a discrete population of baseline potassium channels.
Anesthesiology 85:889-900.
Winegar BD, Yost CS. 1998. Volatile anesthetics directly activate baseline
S K+ channels in aplysia neurons. Brain Res 807:255-262.
Winlow W, Yar T, Spencer G, Girdlestone D, Hancox J. 1992. Differential
effects of general anaesthetics on identifi ed molluscan neurones in situ
and in culture. Gen Pharmacol 23:985-992.
Woolf CJ, Walters ET. 1991. Common patterns of plasticity contributing to
nociceptive sensitization in mammals and Aplysia. Trends Neurosci 14:
74-78.
Young JZ. 1961. Learning and discrimination in the octopus. Biol Rev 36:
32-95.
Young JZ. 1963. The number and size of nerve cells in octopus. Proc Zool
Soc Lond 140:229-254
Zecevic D, Djurisic M, Cohen LB, Antic S, Wachowiak M, Falk CX,
Zochowski MR. 2003. Imaging nervous system activity with voltage-
sensitive dyes. Curr Protoc Neurosci, Chapter 6:Unit 6.17.
... However, the question whether they should be morally considered is rarely addressed. Although the number of works related to this issue has increased over the last years (cfr., for example : Lockwood, 1988;Crook & Walters, 2011;Broom, 2013;Tomasik, 2016dTomasik, [2015 or Knutsson, 2016), the moral consideration of invertebrates is still an important field of animal ethics which remains largely unexplored. The main reason for this seems to be the relatively widespread view of invertebrates as a kind of "aliens" (Lockwood, 2014). ...
... An example is the violent reaction, aimed at evasion, of insects when a needle at high temperature is moved closer to their antenna (Wigglesworth, 1980). The presence of nociception has been established in invertebrates such as snails (Wigglesworth, 1980), fruit flies (Tracey et al., 2003), earthworms (Elwood, 2011), leeches (Broom, 2013), mollusks (Crook & Walters, 2011), octopuses (Mather, 2001), or nematodes (Wittenburg & Baumeister, 1999). In fact, as Feinberg and Mallatt (2016) defend, nociception was even present in the "Cambrian Explosion" in vertebrate ancestors. ...
... However, as Mather (2001) clarifies, nociception is a necessary but not sufficient condition for the existence of subjective experiences in general, and for the experience of pain in particular. In fact, nociceptive responses may even occur without subjective experience in the case of human beings (Crook & Walters, 2011). ...
Article
Full-text available
Invertebrate animals are usually seen as a kind of “aliens” which do not deserve any moral consideration. However, there is a growing amount of evidence indicating that many of them do have the capacity to experience pain. The same criteria that are usually applied in order to infer that vertebrates are sentient beings (behavioral response, learning capacity, memory, a certain specific neurophysiological structure…) lead to the idea that many invertebrates are sentient as well. Therefore, under the skeptical premise that we have no direct evidence of the experience of pain in vertebrates, we are forced to hold that it exists in both vertebrates and invertebrates.
... As we will also see in the following discussions of insects, we should be open to the existence of all kinds of negatively valenced states, and not limit them to human-like cases of pain involving rich sensory representation. Crook and Walters (2011), for instance, argues that gastropods show nociceptive sensitization, which Godfrey-Smith (2020b) describes as "a heightened sensitivity after damage" (p. 1155) and sees as compelling evidence for perhaps a minimal sense of evaluative experience. ...
... What this work has shown is that when gastropods are exposed to aversive stimuli such as electric shocks, they not only react to this with an immediate behavioral response, but there also appears to be a long-term change in behavioural 'character'. Crook and Walters (2011) argue that Aplysia show a conditioned fear-like motivational state when exposed to neutral chemosensory stimuli such as a touch when it has in the past been associated with an electric shock (p. 189). ...
Article
In order to develop a true biological science of consciousness, we have to remove humans from the centre of reference and develop a bottom-up comparative study of animal minds as Donald Griffin intended with his call for a ‘cognitive ethology’. In this article, I make use of the pathological complexity thesis (Veit 2022a,c,b) to show that we can firmly ground a comparative study of animal consciousness by drawing on the resources of state-based behavioral life-history theory. By comparing the different life histories of gastropods and arthropods, we will be able to make better sense of the possible origins of consciousness and its function for organisms in their natural environments.
... Probably experience pain like mammals (Stoskopf 1994;Varner 2012) Fishes Probably experience pain like mammals (Braithwaite 2010;Bovenkerk and Meijboom 2012;Brown 2015;Chandroo et al. 2004;Elder 2014;Varner 2012) Cephalopods (squid) Highly sophisticated and poorly understood nervous system, added to list of sentient animals in European animal experiment legislation (Crook and Walters 2011;Fiorito et al. 2014) Other molluscs (oysters, mussels, snails, sea slugs etc.) ...
... Motivational states and cognitive capabilities in some species that may be consistent with capacity for states with functional parallels to pain (e.g. avoiding food previously combined with electric shock) (Crook and Walters 2011) Crustaceans (crabs, lobsters, crayfish, shrimp) ...
Article
Full-text available
The aim of this paper is to take normative aspects of animal welfare in corporate practice from a blind spot into the spotlight, and thus connect the fields of business ethics and animal ethics. Using insights from business ethics and animal ethics, it argues that companies have a strong responsibility towards animals. Its rationale is that animals have a moral status, that moral actors have the moral obligation to take the interests of animals into account and thus, that as moral actors, companies should take the interests of animals into account, more specifically their current and future welfare. Based on this corporate responsibility, categories of corporate impact on animals in terms of welfare and longevity are offered, including normative implications for each of them. The article concludes with managerial implications for several business sectors, including the most animal-consuming and animal-welfare-threatening industry: the food sector. Welfare issues are discussed, including the issue of killing for food production.
... For rats (Roughan and Flecknell, 2006), mice (Wright-Williams et al., 2007), rabbits , and zebrafish (Sneddon, 2019) specific pain behaviors have been described. Striking painful body part against surface has been used as an indicator of pain in rats (Roughan and Flecknell, 2006) and rabbits and behavior changes caused by noxious stimuli have been demonstrated in several aquatic species including cephalopods (Crook et al., 2014;Crook and Walters, 2011), hermit crabs (Magee and Elwood, 2016), and several species of fish including rainbow trout (Sneddon et al., 2003) and zebra fish (Thomson et al., 2020;. Pain assessment by facial grimace scoring has been validated and showed to be a reliable method for pain assessment in several species (Langford et al., 2010;Keating et al., 2012;Sotocinal et al., 2011;Hageri et al., 2017;, and some traits seems to be conserved across species. ...
Chapter
The aim of this chapter is to provide the reader with guidance and relevant sources related to implementation of animal welfare in husbandry practices, design, and daily operations of animal facility. Specifically, the authors aim to address the following key requirements as indicated in the Directive 2010/63: -To indicate how good welfare can promote good science, e.g., how the failure to attend to biological and behavioral needs may affect the outcome of procedures. -To indicate how husbandry and care may influence experimental outcome and the number of animals needed, e.g., example where the place in the room influences the outcome, hence randomization. -To describe the dietary requirements of the relevant animal species and explain how these can be met. -To describe the importance of providing an enriched environment (appropriate to both the species and the science) including social housing and opportunities for exercise, resting, and sleeping. -To describe suitable routines and husbandry practices for the maintenance, care, and welfare for a range of animals used in research, to include small laboratory species and large animal species where appropriate. -To describe suitable environmental and housing conditions for laboratory animals, how conditions are monitored, and identify the consequences for the animal resulting from inappropriate environmental conditions. -To recognize that changes to or disruption of circadian or photoperiod can effect animals. -To describe the biological consequences of acclimatization, habituation, and training. -To describe how to provide water and an appropriate diet for laboratory animals including the sourcing, storage, and presentation of suitable foodstuffs and water.
... However, recent studies are continuously discovering and coming to a consensus that some marine invertebrates perceive painlike sensations through nociceptive reflexes, albeit in different ways than mammals (Sneddon, 2015). Their cognitive abilities may also be more extensive than previously thought and some can change their behavior to avoid pain stimuli after one exposure (Mather and Anderson, 2007;Crook and Walters, 2011). Sneddon (2015) also found that the green crab, Carcinus maenas, shows behavioral shifts to avoidance during electroshock, suggesting preliminary evidence of nociception in crustaceans. ...
Article
Full-text available
Making up over 92% of life in our oceans, marine invertebrates inhabit every zone in the water column, with contributions ranging from ecosystem functioning to socioeconomic development. Compared to charismatic species, marine invertebrates are often underrepresented in IUCN reports and national conservation efforts. Because of this, as climate change intensifies in conjunction with increasing anthropogenic pressures such as habitat destruction, many marine invertebrates are at risk of silently heading toward extinction. However, public perception has shifted in recent years due to the growing awareness of the important roles these invertebrates play in marine and human life. This change may promote greater support for future research and conservation campaigns of key species. This review highlights the importance of marine invertebrates, the environmental and anthropogenic stressors they are currently facing, and the inherent challenges in their successful conservation. Potential solutions to fill the gaps in current knowledge will be also explored in the context of recent globalization and technological advancements. The loss of marine invertebrate biodiversity will have cascading ecological, economic, and sociological repercussions, so compiling key information into a holistic review will add to the conversation of the importance of global marine invertebrate conservation.
... No matter what public opinion is, nociception has been seen in invertebrates and thus the welfare of these animals must be considered in the laboratory. 24,35,80,83,109 Further reading is encouraged through Harvey-Clark (2011) for interested audiences. 35 During the early development of this study our institution's IACUC o ce was consulted. ...
Preprint
Full-text available
Crayfish (Decapoda: Astacoidea & Parastacoidea), are amongst the few animals that have stem cells within hemolymph, with the capacity to continuously produce differentiated neuronal structures throughout life. As crayfish and other invertebrates continue to become common models in research to study human disease, it is vital that we develop universal laboratory standards and guidelines on housing and husbandry practices. This publication presents introductory data on housing, husbandry, hemolymph collection and statistically supported anesthesia trials, to support future research endeavors. Evaluation of housing, husbandry, clinical and anesthetic techniques in Procambarus clarkii maintained in a biomedical research setting were performed. An option for hemolymph collection, in the area termed, the Ventral Coelomic Hemolymph Collection Zone (VCHCZ) is presented as a technique to assess hemocytes. Additionally, Wright Giemsa stained slides of crayfish hemolymph were evaluated by a board-certified veterinary clinical pathologist for interpretation and confirmation of hemolymph collection. The housing and husbandry experiments were performed over a duration of 37 days. Mortality rates and physical health assessments were performed. The following water quality parameters were concurrently evaluated: temperature, light cycle, pH, KH, GH, conductivity, total dissolved solids, salinity, ammonia, nitrite, and nitrate. Anesthetic techniques were evaluated between four experimental groups: (A) immersion in buffered MS-222 (50 mg/L), (B) immersion in buffered MS-222 (150 mg/L) (C) immersion in Propofol (65 mg/L) and (D) Propofol injection (100 mg/kg) into VCHCZ. Housing and husbandry techniques were validated with 0% mortality and normal species-specific behaviors were observed. MS-222 immersion had no observable effect on crayfish. Propofol immersion (65 mg/L) created sedative effects allowing for appropriate handling. Propofol injection (100 mg/kg) into VCHCZ successfully created a deep anesthetic plane that would allow for more invasive or surgical procedures, without adverse effects during or after recovery.
Chapter
Cephalopods are an interesting and diverse group of animals in nature, and their dexterity, speed, unique anatomical features, colorful beauty, visual acuity, and ability to learn various tasks make them popular with the communication media and public in general. Cephalopods are members of the phylum Mollusca and share basic body organizational features with the gastropods, bivalves, and other mollusks. The octopuses are represented by several families and have a worldwide distribution. The cephalopod immune system can be compromised easily with poor water quality, overcrowding, and/or increased bacterial load on the aquatic system. Disease management of captive cephalopods depends on careful and attentive husbandry with high-quality nutrition, frequent clinical assessment and observation of animals, and appropriate use of antibiotics. The best approach in the treatment of cephalopods is the careful monitoring and control of water quality. Since the high surface area skin has a microvillus border, drugs may be readily absorbed, and possibly at toxic levels.
Technical Report
Full-text available
Sentience is the capacity to have feelings, such as feelings of pain, pleasure, hunger, thirst, warmth, joy, comfort and excitement. It is not simply the capacity to feel pain, but feelings of pain, distress or harm, broadly understood, have a special significance for animal welfare law. Drawing on over 300 scientific studies, we have evaluated the evidence of sentience in two groups of invertebrate animals: the cephalopod molluscs or, for short, cephalopods (including octopods, squid and cuttlefish) and the decapod crustaceans or, for short, decapods (including crabs, lobsters and crayfish). We have also evaluated the potential welfare implications of current commercial practices involving these animals.
Article
Welfare within zoos and aquariums has come under increasing scrutiny due to the change in public opinion of animals in captivity. It is vital that as an industry mechanisms and frameworks are in place to determine welfare of animals within our care. Due to potential bias in current welfare models toward terrestrial vertebrates, it is important to determine whether they can be utilised in differing environments such as aquariums. Using the most recent five domain model (Mellor, 2017) the possible application within public aquaria is discussed, considering each domain in respect to aquatic invertebrates, an often-neglected group of organisms when considering welfare in aquaria. This review highlights the additional considerations needed when applying the five domain model to this diverse group of organisms. Furthermore, the identification of gaps within the current literature is discussed in respect to whether the full five domain model can be currently be applied at this time.
Chapter
Eine fundamentale Erkenntnis aus der Evolutionsforschung ist, dass die Lebensvorgänge aller Organismen vergleichbar sind, weil sie letztlich aus physiologischen Prozessen gemeinsamer Vorfahren entstanden sind. Für die vergleichende Sinnesphysiologie, die sich mit den Gewebetieren (Eumetazoa) beschäftigt, bedeutet diese Vergleichbarkeit, dass sensorische Prozesse im gesamten Tierreich nach den gleichen Prinzipien ablaufen. Auf den ersten Blick mag eine solche Abschätzung absurd erscheinen. Was schließlich hat die Berührungsempfindlichkeit eines Fadenwurmes mit dem Tastsinn einer Maus zu tun? Je genauer man aber hinschaut, desto deutlicher treten Gemeinsamkeiten hervor, und der Nachweis gemeinsamer genetischer Merkmale reicht heute schon in präkambrische Zeiten zurück, also in Zeiträume lange vor der Diversifizierung der heute lebenden Tierstämme. Tatsächlich erscheinen uns die Gemeinsamkeiten der Augen von Quallen, Muscheln, Perlbooten, Haien und Vögeln offensichtlich, obwohl diese Tiergruppen keineswegs in gemeinsamen Entwicklungslinien stehen. Trotzdem zeigen sie Ähnlichkeiten sowohl in ihrer genetischen Ausstattung als auch bei der Strukturierung und der Funktion ihrer Augen. Es ist in diesem Zusammenhang unerheblich, inwieweit Sinnesorgane durch monophyletische oder polyphyletische Evolutionsprozesse entstanden sind; die Ähnlichkeiten in Struktur und Funktion bilden die Basis sinnvoller Vergleiche. Wir können davon ausgehen, dass sensorische Prozesse erkennbare Parallelen bei allen Tieren aufzeigen, dass sie aber darüber hinaus durch Anpassungen an die arttypischen Erfordernisse geformt worden sind.
Article
Full-text available
Defensive responses to noxious stimulation are found throughout the animal kingdom, and nociceptors that detect incipient injury have been reported in species representing most of the major animal phyla. Emerging molecular genetic evidence indicates that at least some nociceptive transduction mechanisms have been widely conserved during evolution, notably mechanisms involving the degenerin/epithelial Na+ channel and transient receptor potential families of ion channels. Nociceptive neural networks show similarities across many species, including the use of inhibitory mechanisms to produce antinociception during active escape behavior. However, opiates and melanocortin receptors, as well as the mas-related genes family of receptors, may be restricted to the chordate lineage. Long-lasting, nociceptive sensitization often follows the antinociceptive phase after peripheral injury, and some mechanisms underlying this sensitization are conserved across phyla. Some of these are involved in plasticity of nociceptor synapses (N-methyl-d-asparate-receptor-dependent low-term synaptic potential) and regulation of gene transcription in nociceptive pathways (CREB activation). Knowledge gained from investigating homologous nociceptive mechanisms in various phyla can offer useful insights into how these mechanisms operate in humans. Comparative studies may also provide clues about the evolution of emotional aspects of pain, although subjective pain experiences in animals are not directly accessible for experimental investigation.
Chapter
This introductory chapter explains the coverage of this book, which is about the phylogeny and evolution of the members of phylum Mollusca. It explains that the Mollusca are the second largest phylum of animals, with about 200,000 living species and that they have a remarkable fossil record reaching back to the earliest Cambrian period. This book represents the works of thirty-six different contributors from eleven countries and it reflects the globalization of molluscan evolutionary studies that has taken place during the last fifty years.