Giancarlo Carli

Università di Pisa | UNIPI · Department of Translational Research on New Technologies in Medicine and Surgery

Objectives: Although neurobiological research has shown that interoception plays a role in the perception of pain and its chronification, the relationship between interoceptive sensitivity and pain has not been definitively confirmed by clinical studies. The aim of this study was therefore to better understand the relationship between interoceptiv...

The most widely used formalin test to screen antinociceptive drug candidates is still apostrophized as targeting inflammatory pain, in spite of strong opposing evidence published. In our rat skin-nerve preparation ex vivo, recording from all classes of sensory single-fibers (n = 32), 30 units were transiently excited by formaldehyde concentrations...

We propose here an evolutionary interpretation of the presence of highly hypnotizable persons (highs) among the general population. Current experimental evidence suggests the presence of stronger functional equivalence between imagery and perception, non-opioid cognitive control of pain, favorable cardiovascular asset, and greater interoceptive sen...

Objectives Somatosensory amplification (SA) has been described as an important feature of somatoform disorders, and an “amplifying somatic style” has been reported as a negative connotation of body perception. As widespread pain (WSP) in fibromyalgia (FM) is due to a central sensitization (CS) rather than organic alterations, there has been discuss...

Fatty acid amide hydrolase (FAAH) degrades the endogenous endocannabinoid (eCB) anandamide and might be involved in the response to suggestions of analgesia in subjects with high hypnotizability scores (highs). Since the A allele of the FAAH C385A polymorphism (rs324420) is associated with lower FAAH activity, it was studied in 21 highs, 66 low hyp...

Aim: Somatosensory amplification (SSA) is defined as the tendency to experience somatic sensation as intense, noxious, and disturbing, and plays as critical role in the pathophysiology of somatisation (Barsky et al., 1988). In turn, dysfunctional sensory modulatory processing seems to be involved in the pathophysiology of SSA (Perez et al., 2015)....

The study investigated whether the cardiac activity and cognitive–emotional traits sustained by the behavioral inhibition/activation system (BIS/BAS) may contribute to hypnotizability-related pain modulation. Nociceptive stimulation (cold-pressor test) was administered to healthy participants with high (highs) and low (lows) hypnotizability in the...

In the general population, transcranial anodal direct current stimulation of the cerebellum (ctDCS) reduces pain intensity and the amplitude of nociceptive laser evoked potentials (LEPs), whereas cathodal ctDCS elicits opposite effects. Since behavioral findings suggest that the cerebellar activity of highly hypnotizable individuals (highs) differs...

The aim of the present study was to compare the effects of explicit suggestions of analgesia and of the activation of the Diffuse Noxious Inhibitory Control (DNIC) by cold pressor test on pain perception and heart rate in healthy participants with high (highs, N=18), low (lows, N=18) and intermediate scores of hypnotizability (mediums, N=15) out of...

We evaluated the role of cerebellum in defensive responses, by recording the Hand Blink Reflex (HBR) and modulating cerebellar activity with transcranial Direct Current Stimulation (tDCS). The active electrode was centered on the median line 2 cm below the inion and the return one over the right shoulder. Direct current was applied for 20 min with...

The cerebellum is involved in a number of integrative functions, but its role in pain perception and nociceptive processing is poorly understood. We evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying changes in perceptive threshold (PT), pain intensity (VAS) and laser evoked potentials (LEPs). Twenty-fiv...

Melatonin (MLT) is a neurohormone with significant involvement in several biological functions, of which antinociception and tonic immobility (TI) may be the key neurobehavioral components to survive in adverse conditions such as a predator attack. TI-induced antinociception can be elicited, facilitated, or increased through opioid and γ-aminobutyr...

The cerebellum is involved in a wide number of integrative functions, but its role in pain experience is poorly understood. We evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in the perceptive threshold, pain intensity (VAS:0-10) and laser evoked potentials (LEPs) variables. Twenty-five su...

Objective The cerebellum is involved in a wide number of integrative functions, but its role in pain perception and nociceptive processing is poorly understood. We evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in perceptive threshold (PT), pain intensity (VAS) and laser evoked potentials...

The susceptibility to hypnosis, which can be measured by scales, is not merely a cognitive trait. In fact, it is associated with a number of physiological correlates in the ordinary state of consciousness and in the absence of suggestions. The hypnotizability-related differences observed in sensorimotor integration suggested a major role of the cer...

The cerebellum is involved in a wide number of integrative functions, but its role in pain experience and in the nociceptive information processing is poorly understood. In healthy volunteers we evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in the perceptive threshold, pain intensity at...

Abstract. Purpose: The cerebellum is involved in a wide number of integrative functions, but its role in pain experience and in the nociceptive information processing is poorly understood. In healthy volunteers we evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in the perceptive threshold,...

Objective. The aim of the study was to compare the pain symptoms of fibromyalgia patients exhibiting (FMS+PVD) and not exhibiting (FMS) comorbidity with provoked vulvodynia. Study Design. The case control study was performed in 39 patients who had been diagnosed with FMS and accepted to undergo gynaecological examination and in 36 healthy women (C)...

Higher brain dopamine content depending on lower activity of Catechol-O-Methyltransferase (COMT) in subjects with high hypnotizability scores (highs) has been considered responsible for their attentional characteristics. However, the results of the previous genetic studies on association between hypnotizability and the COMT single nucleotide polymo...

The formalin test still surprises with its biphasic pain-related behavior resulting from a quiescent interphase which does not occur with other algogenic compounds and remains unexplained. The first phase has been attributed to TRPA1-mediated excitation of nociceptors, the second phase to their inflammatory and/or spinal sensitization. We show that...

In healthy subjects with high hypnotisability (highs) under hypnosis, subjectively effective suggestions for analgesia abolish the increases in blood pressure associated with cold pressor test (cpt) by reducing the peripheral vascular resistance. The aim of the present study was to investigate the effects of the suggestions of analgesia on the resp...

The cognitive trait of hypnotizability, associated with the proneness to accept suggestions, exhibits several physiological correlates including the modulation of sensorimotor integration and, in particular, of postural control. In this respect, we have shown that, at eyes closure, healthy subjects with high hypnotizability scores (highs) having th...

The aim of the study was to test the efficacy of pain imagery as a function of hypnotisability and of the activity of Behavioral Inhibition/Activation Systems. Questionnaires of imagery abilities (Betts) for the visual, cutaneous and organic modalities, absorption in cognitive tasks (TAS), proneness to inhibit stressful/painful experience/seek out...

Mean values and the spectral variability of heart rate (HRV), blood pressure, and skin blood flow were studied in high and low hypnotizable subjects during simple relaxation. Similar subjective relaxation was reported by highs and lows. A parasympathetic prevalence (indicated by a higher High-Frequency component of HRV and a lower High/Low-Frequenc...

The cognitive trait of hypnotizability modulates sensorimotor integration and mental imagery. In particular, earlier results show that visual recognition of 'nonmeaningful', unfamiliar objects bimanually explored is faster and more accurate in subjects with high (Highs) than with low hypnotizability (Lows). The present study was aimed at investigat...

the purpose of this study was to introduce new procedure to determine the magnitude of functional recovery after knee surgery. we compared the performance in the leg extension test and the response in the sEMG activity to vibration in the operated to the non-operated leg. Thirty-eight patients with knee operation and 14 healthy subjects participate...

The study analyzed the writing products of subjects with high (highs) and low (lows) hypnotizability. The participants were asked to write short texts in response to highly imaginative scenarios in standard conditions. The texts were processed through computerized and manual methods. The results showed that the highs' texts were more sophisticated...

The initial section summarizes the three conflicting concepts about pain already present at the end of the nineteenth centuries, i.e., the Specificity Theory, the Intensive-Summation Theory and the Pleasure Pain Theory and illustrates how, in the following decades, new experimental results partially support other innovative theories such as the Pat...

It has been shown that, in subjects with high hypnotizability (Highs), imagined somatosensory stimulation can involuntarily activate the neural circuits involved in the modulation of reflex action. In this vein, aim of the study was to investigate whether the imagery of nociceptive stimulation in one leg may produce both subjective experience of pa...

The study assessed differences between highly (Highs) and low hypnotizable (Lows) subjects in the blindfolded reproduction of paths connected at acute or obtuse angles. Reproduction attempts were made after path exploration performed by one finger, with or without concomitant cognitive activities (mental computation or imagery of exploring an angle...

Hypnotizability is associated with peculiar characteristics of sensorimotor integration, imaginal abilities, and preferences in the sensory modality of imagery. The visual recognition of haptically explored objects involves an interaction among these processes and is a proper tool to investigate their possible hypnotizability-related modulation. Si...

Previous studies showed that highly hypnotizable persons imagining a specific sensory context behave according to the corresponding real stimulation and perceive their behaviour as involuntary. The aim of the study was to confirm the hypothesis of a translation of sensory imagery into real perception and, thus, of a true involuntary response. We st...

Body sway and locomotion are differentially modulated in high (highs) and low (lows) hypnotizable subjects undergoing alteration of visual and neck/leg proprioceptive inputs. The study's aim was to investigate whether partial impairment of vestibular information due to backward head extension affects postural (Study 1) and locomotor behavior (Study...

Hypnotizability is a cognitive multidimensional trait that involves peculiar imagery characteristics. Subjects with high- (Highs) and low (Lows)-susceptibilities to hypnosis have shown different levels of skill at visual and somesthetic-guided imageries performed during upright stance. The aim of this experiment is to study the modulation of the EE...

Dietary supplementation of omega-3 (n-3) is becoming increasingly popular as a complementary treatment of chronic inflammatory pain diseases. The aim of the present study was to examine the effects of short-term (35 days) n-3 supplementation on physiological/psychophysical variables and clinical symptoms in patients with musculoskeletal pain and fi...

In highly hypnotizable individuals (highs), postural control is more independent of sensory information than in low hypnotizable subjects (lows). The aim of the study was to find out whether locomotion is also less affected in highs than in lows by visual suppression and changes in the neck proprioceptive input. Eighteen highs and 20 lows were aske...

Hypnotizability is a cognitive trait measured by standard scales and associated with peculiar physiological responses to cognitive and physical stimulations. Hypnotizability-related differences can also be observed in non-hypnotic state and in the absence of specific suggestions. In the normal bipedal stance subjects with high hypnotizability (High...

In this study, we aimed at comparing the effect of the social versus the physical enrichment of the environment on inflammatory pain. Hence, a rat model of carrageenan-induced knee inflammation was used. Four housing conditions were investigated: a physically enriched environment (PE), a socially enriched environment (SE), an enriched environment (...

Hypnotizability is associated with a few physiological characteristics also in the normal awake state. Differences in flow-mediated dilation (FMD) have been observed in subjects with high (Highs) or low (Lows) hypnotizability during nociceptive stimulation. FMD is largely due to the nitric oxide (NO) produced by vascular endothelium through the act...

Alexithymia, a lack of emotional awareness, is common in chronic pain patients. The aim of the study was to investigate the relationship of alexithymia to ongoing pain, experimental pain sensitivity, and illness behavior in patients with chronic musculoskeletal pain. Sixty-eight women with fibromyalgia (age: average, 43.4 years; range, 19-72 years)...

Aim of the experiment was to study whether cognitive load affects postural control more in low (Lows) than in highly hypnotizable (Highs) subjects due to the latter's greater attentional abilities. Standing Highs and Lows underwent an experimental session (closed eyes) consisting of a basal condition and of mental computation in an easy (stable sup...

Aim of the experiment was to study whether cognitive load affects postural control more in low (Lows) than in highly hypnotizable (Highs) subjects due to the latter’s greater attentional abilities. Standing Highs and Lows underwent an experimental session (closed eyes) consisting of a basal condition and of mental computation in an easy (stable sup...

The aim of the present review is to discuss two interesting hypotheses that explain the pathophysiology of pain: (1) Arthur Craig's hypothesis that the experience of pain, elicited by specific sensors projecting into the central nervous system through afferent pathways, is relevant for homeostasis and represents a specific emotion related to a home...

The aim of the present study was to investigate the long-term efficacy of a 3-week intensive residential multidisciplinary non-pharmacological treatment program (including individually prescribed and monitored aerobic exercise and cognitive behavioural therapy) on fibromyalgia symptoms and aerobic fitness. Twenty-five women with fibromyalgia partic...

The aim of the experiment was to investigate whether the peculiar attentional/imagery abilities associated with susceptibility to hypnosis might make postural control in highly hypnotizable subjects (Highs) that are less vulnerable to sensory alteration than in individuals with low hypnotic susceptibility (Lows). The movement of the centre of press...

Heart rate and heart-rate variability (HRV) were studied through a set of different methods in high (highs) and low hypnotizable subjects (lows) not receiving any deliberate hypnotic induction in basal conditions (simple relaxation) and during nociceptive-pressor stimulation with and without suggestions of analgesia. ANOVA did not reveal any differ...

The study investigated the differences in pain perception in highly (Highs) and low (Lows) hypnotizable patients with chronic benign pain undergoing hypnotic suggestions of analgesia. Self reports of pain intensity were collected in different groups of fibromyalgic patients: (1) Highs and Lows during pre-hypnosis, neutral hypnosis, suggestions for...

We discuss the role of hypnotizability in the development and treatment of chronic pain, and in the prognosis of its possible cardiovascular consequences. Data indicate that high hypnotic susceptibility is not necessary for the relief of chronic pain obtained through hypnotic treatment. Moreover, and at variance with an earlier hypothesis, being hi...

Hypnotizability is a cognitive trait able to modulate many behavioural/physiological processes and associated with peculiar functional characteristics of the frontal executive system. This review summarizes experimental results on hypnotizability-related differences in sensorimotor integration at a reflex and an integrated level (postural control)...

To date, few results on well-being in chronic-pain patients have been published, while several studies in patients without pain have indicated that well-being may not be equivalent to absence of psychological distress. The aim of the present study was to investigate the relationship between psychological distress and well-being and to identify the...

The use of unidimensional scales to measure pain intensity has been criticised because of the multidimensional nature of pain. We conducted multiple linear regression analyses to determine which dimensions of pain--sensory versus affective--predicted scores on unidimensional scales measuring pain intensity and emotions in 109 Italian women sufferin...

Imagery plays an important role in hypnotic phenomena. Recent findings have shown, however, that hypnotized subjects with high (Highs) and low (Lows) susceptibility to hypnosis undergoing guided imagery tasks centred on specific sensory modalities share similar visual imagery ability, but Highs obtain better imagery than Lows when tactile instructi...

Postural control in subjects with high (Highs) and low (Lows) susceptibility to hypnosis is differentially affected by changes in visual and neck tactile/proprioceptive input. The aim of the present experiment was to investigate whether imagery of the visual and tactile sensory modalities also induces different modulation of postural control in Hig...

The aim of the present study was to investigate the effects of a 3-week residential multidisciplinary non-pharmacological treatment program (including individually prescribed aerobic exercise and cognitive-behavioral therapy) on fibromyalgia symptoms and hypothalamic-pituitary-adrenal (HPA) axis function. Salivary and venous blood samples were coll...

Hypnotic suggestions describing an altered perception induce congruent changes in the subject's experience and behavior. However, it is not known whether an implicit suggestion, only indirectly referring to an altered perception, induces a behavioral response corresponding to that of the real situation. In this study, an implicit suggestion of back...

Mental stress induces endothelial dysfunction, that is a reduction of the post-occlusion brachial artery flow-mediated vasodilation (FMD). This does not occur in subjects highly susceptible to hypnosis (Highs) in either the waking or hypnotic state. The aim of the present experiment was to assess whether endothelial dysfunction is also induced by a...

Neural mechanisms of muscle pain Action potentials originating from nociceptors carry information about noxious stimuli, but the perception of pain from muscles is the end product of information processing in the central nervous system (CNS). Nociceptors In skeletal muscles, there are three types of nociceptors that encode the intensity of noxious...

The aim of the present study was to investigate the possible hypnotizability-related modulation of heart activity during nociceptive stimulation (pressor pain) and during nociceptive stimulation associated with the suggestion of analgesia in not hypnotized healthy individuals with a high (Highs) and a low (Lows) hypnotic susceptibility. ECG and res...

Subjects highly (Highs) and low susceptible to hypnosis (Lows) show different imagery and attentional capabilities and also peculiar somatomotor, vegetative and electroencephalographic differences in basal and task conditions. Since attention is one of the main component of hypnotic susceptibility and also a relevant factor for postural control, th...

The aim of the experiment was to assess whether the membrane excitability of flexor cervical and/or lumbar motoneurons is related to hypnotic susceptibility (measured with the Stanford Hypnotic Susceptibility Scale, Form A) and hypnosis. During the experimental sessions, hypnotized subjects were given only suggestions of relaxation (neutral hypnosi...

In this study, we evaluated pain sensitivity in patients with fibromyalgia or other types of chronic, diffuse musculoskeletal pain to establish whether fibromyalgia represents the end of a continuum of dysfunction in the nociceptive system. One hundred and forty five patients and 22 healthy subjects (HS) completed an epidemiological questionnaire t...

Sensory neurons responding to stimuli capable of producing tissue damage are termed nociceptors and have free nerve endings of either myelinated small-diameter (Aδ) or unmyerlinated (C) fiber axons. They display either single or multiple receptive fields. Nociceptive afferents supply skin, subcutaneous tissue, periosteum, joints, muscles and viscer...

This chapter discusses neuroplasticity and clinical pain. Clinical pain is a complex experience with several qualities, including sensory-discriminative, motivational-affective, and cognitive-evaluative aspects. The chapter illustrates that pain associated with tissue or nerve lesions may cause emotional changes and that psychological factors, even...

Introduction. The classification of the American College of Rheumatology (ACR) for fibromyalgia takes into account some quantitative aspects of pain, such as intensity, duration, diffusion and reactivity to mechanical pressure stimuli in tender points. According to the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), the Pain Disord...

In the present investigation, the antinociceptive effects of the muscarinic cholinergic agonist, oxotremorine, were evaluated in rats using the formalin test. In Expt. 1, two oxotremorine concentrations (0.1 and 0.2 mg/kg) and two administration times (15 and 1 min before formalin injection) were chosen. All spontaneous and formalin-evoked behavior...

In the present investigation, the antinociceptive effects of the muscarinic cholinergic agonist, oxotremorine, were evaluated in rats using the formalin test. In Expt. 1, two oxotremorine concentrations (0.1 and 0.2 mg/kg) and two administration times (15 and 1 min before formalin injection) were chosen. All spontaneous and formalin-evoked behavior...

The aim of the present study was to evaluate the response of adrenocorticotropin ([ACTH]) and growth hormone ([GH]) concentrations to a typical aerobic swimming set during a training season. Nine top-level male endurance swimmers (age range 17–23 years) were tested during three training sessions occurring 6, 12 and 18 weeks after the beginning of t...

Nociceptive electrical stimuli were applied to the sural nerve during hypnotically-suggested analgesia in the left lower limb of 18 highly susceptible subjects. During this procedure, the verbally reported pain threshold, the nociceptive flexion (RIII) reflex and late somatosensory evoked potentials were investigated in parallel with autonomic resp...

In vivo microdialysis was used to assess the effects of Novelty, persistent pain (Formalin test) and stress (Restraint) on hippocampal acetylcholine (ACh) release. Experiments were carried out during the dark phase, i.e. during the active period of the animal, and consisted of four experimental phases: Baseline (30 min), Novelty (30 min), Formalin...

Different approaches to the study of the relationship between hippocampal electrical activity and behavior have shown that hippocampal EEG varies according to different behavioral aspects. In particular, a rhythmic slow activity (RSA, Theta rhythm) can be recorded during voluntary movements and to a lesser degree during immobility. In laboratory ex...

The influence of psychological factors and of pain intensity on analgesic performance was studied in a clinical setting in which cognitive activity was emphasized. Thirty-eight patients who underwent thoracotomy were investigated. Before surgery, we administered purpose-designed questionnaires and psychological tests to investigate the patient's pa...