Jana Sawynok

Jana Sawynok
Dalhousie University | Dal · Department of Pharmacology

PhD

About

195
Publications
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Introduction
Jana Sawynok, Department of Pharmacology, Dalhousie University. Research interests involve development of novel therapies for chronic pain. In the past, this has involved exploring adenosine and caffeine, and topical analgesics. More recent additional interests include complementary practices for chronic pain, including qigong.

Publications

Publications (195)
Article
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Qigong, which can be characterized in many different ways, is offered as a complementary self-care practice at a tertiary-care pain management unit in Halifax, Nova Scotia. This report provides a quantitative and qualitative assessment of two groups engaged in qigong practice in this context as part of two Research in Medicine (RIM) projects (2014-...
Article
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The Pharmacological Society of Canada (PSC) formed in 1956 and became a constituent society of the Canadian Federation of Biological Sciences (CFBS) in 1958. Over subsequent decades, it met annually with CFBS, matured as a society, and established an identity as the voice of pharmacology in Canada. During the 1980s, it sought a larger stage and bid...
Article
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Qigong is an internal art practice with a long history in China. It is currently characterized as meditative movement (or as movement-based embodied contemplative practice), but is also considered as complementary and alternative exercise or mind–body therapy. There are now six controlled trials and nine other reports on the effects of qigong in fi...
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Cancer pain considered as neuropathic can occur in up to 40% of cancer patients and impair quality of life. Neuropathic cancer pain is treated using therapies with proven efficacy in other neuropathic pain (NeP) conditions including adjuvants such as tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, gabapentinoids, and other a...
Article
Introduction: Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option. Areas covered: This report summarizes both published and unpublished results...
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Fibromyalgia (FM) is characterized by widespread pain and multiple other symptoms; underlying mechanisms include central sensitization, dysregulation of the stress response system, and autonomic nervous system dysregulation. Alterations in the sympathetic nervous system have been variably implicated, but a reduction in parasympathetic nervous syste...
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The main focus for development of adenosine targets as analgesics to date has been A1Rs due to its antinociceptive profile in various preclinical pain models. The usefulness of systemic A1R agonists may be limited by other effects (cardiovascular, motor), but enhanced selectivity for pain might occur with partial agonists, potent and highly selecti...
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Introduction. Qigong is currently considered as meditative movement, mindful exercise, or complementary exercise and is being explored for relief of symptoms in fibromyalgia. Aim. This narrative review summarizes randomized controlled trials, as well as additional studies, of qigong published to the end of 2013 and discusses relevant methodological...
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Neuropathic pain (NeP) is a significant medical and socioeconomic burden with limited therapeutic options. Elderly patients exhibit a higher incidence of several NeP conditions and pose a particular challenge due to age-related pharmacokinetic and pharmacodynamic issues, comorbid conditions, and polypharmacy, as well as frailty and cognitive declin...
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Objectives: A randomized controlled trial (RCT) and an extension trial of qigong (Chaoyi Fanhuan qigong [CFQ]) in patients with fibromyalgia were recently completed. In the present study, a qualitative analysis of comments from the RCT was undertaken using motivation and amount of practice to determine whether initial experiences provided informat...
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Inosine is an endogenous nucleoside that has anti-inflammatory and antinociceptive properties. Inosine is a metabolite of adenosine, and some of its actions suggest the involvement of adenosine A1 receptors (A1Rs). The purpose of this study was to better understand mechanisms of inosine-induced antinociception by investigating the role of A1Rs and...
Article
Ketamine, in subanesthetic doses, produces systemic analgesia in chronic pain settings, an action largely attributed to block of N-methyl-D-aspartate receptors in the spinal cord and inhibition of central sensitization processes. N-methyl-D-aspartate receptors also are located peripherally on sensory afferent nerve endings, and this provided the in...
Article
Topical analgesics applied locally to skin or to specialized compartments modify pain by actions on sensory nerve endings and/or adjacent cellular elements. With this approach, there are low systemic drug levels, good tolerability and few drug interactions, and combination with oral formulations is feasible. The goal of this review is to provide an...
Article
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Adenosine A1 receptors (A1Rs) have been shown to be involved in antinociception in preclinical models for several decades. Thus, systemic, peripheral, spinal, and supraspinal administration of A1R agonists universally produces antinociception in nociceptive, inflammatory, and neuropathic pain models. The clinical potential for adenosine (given intr...
Article
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This extension trial is an open-label observational trial of 20 subjects with fibromyalgia who undertook level 2 Chaoyi Fanhuan Qigong (CFQ) training following an earlier controlled trial of level 1 CFQ. Subjects practiced 60 min/day for 8 weeks and continued some daily practice for 6 months. Quantitative measures, assessed at baseline, 8 weeks, 4...
Article
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Background: Qigong, which has many forms, was recently described as "meditative movement," and represents a self-care technique that can contribute to improved health. There are challenges involved in research into qigong, including defining the amount of instruction required for threshold effects, and whether there is a relationship between amoun...
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Fibromyalgia is difficult to treat and requires the use of multiple approaches. This study is a randomized controlled trial of qigong compared with a wait-list control group in fibromyalgia. One hundred participants were randomly assigned to immediate or delayed practice groups, with the delayed group receiving training at the end of the control pe...
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Previous research suggests that high levels of pain catastrophizing might predict poorer response to pharmacological interventions for neuropathic pain. The present study sought to examine the clinical relevance of the relation between catastrophizing and analgesic response in individuals with neuropathic pain. Clinically meaningful reductions were...
Article
The present study examined effects of caffeine on antinociception by acetaminophen in the formalin test in mice. It demonstrates that caffeine 10mg/kg inhibits antinociception produced by acetaminophen 300 mg/kg i.p. against phase 2 flinches. Chronic administration of caffeine in the drinking water (0.1, 0.3g/l) for 8 days also inhibits the action...
Article
This study examined (a) the effect of formalin administration into two different sensory fields, the lateral and medial hindpaw, in the spared nerve injury (SNI) model in rats and (b) peripheral antinociception by morphine when co-administered with formalin at lateral and medial hindpaw sites. Following SNI and injections into the lateral hindpaw,...
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Caffeine, an antagonist of adenosine A(1), A(2A) and A(2B) receptors, is known as an adjuvant analgesic in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen in humans. In preclinical studies, caffeine produces intrinsic antinociceptive effects in several rodent models, and augments the actions of NSAIDs and acetamino...
Chapter
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Topical analgesics are applied to the skin and produce a localized effect on sensory nerve endings to inhibit pain signaling in the periphery. This approach offers the advantage of few systemic adverse effects. There is clear evidence that topical NSAIDs produce analgesia, especially in osteoarthritis. Topical local anesthetics produce pain relief...
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Caffeine, an antagonist of adenosine A1, A2A and A2B receptors, is known as an adjuvant analgesic in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen in humans. In preclinical studies, caffeine produces intrinsic antinociceptive effects in several rodent models, and augments the actions of NSAIDs and acetaminophen....
Article
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Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an...
Article
Oxcarbazepine is an anticonvulsant drug that has been explored as a novel therapeutic agent to treat neuropathic pain in humans. It produces antinociception in several preclinical models of pain, and these actions are blocked by methylxanthine adenosine receptor antagonists which implicates adenosine it its actions. In this study, the antinocicepti...
Article
Following surgery, nerve injury can lead to persistent neuropathic pain. Pre-emptive and preventive analgesic treatments in the perioperative period aim to minimize nerve injury-induced pain. Here we demonstrate that a perioperative regimen of amitriptyline (10 mg/kg i.p. 30 min before and immediately after surgery, followed by oral amitriptyline 1...
Chapter
Peripheral aspects of sensory nervesAdenosine receptors and sensory neuronsPeripheral pharmacology of adenosine A1 and A2A receptorsPeripheral pharmacology of adenosine A2B and A3 receptorsIndirectly acting agents involving adenosineAdenosine and other pharmacological agentsPotential for development as analgesicsReferences
Article
Background: The primary objective of this study was to examine the differential impact of catastrophic thinking on response to placebo and active treatment in the context of a clinical trial for the treatment of neuropathic pain. Secondary objectives included examination of specific dimensions of catastrophic thinking that influence response to pla...
Article
Local application of alphabetaMeATP (ligand for P2X3 receptors) and capsaicin (ligand for TRPV1 receptors) to the rat hindpaw produces pain behaviors (flinching) which are enhanced by noradrenaline (NA). In this study, we have examined the effect of nerve injury on adrenergic regulation of P2X3 and TRPV1 receptors by administering alphabetaMeATP an...
Article
Amitriptyline is used to treat neuropathic pain in humans. It produces antinociception in several animal models of pain, and this effect is blocked by methylxanthine adenosine receptor antagonists which implicates adenosine it its actions. Here, the antinociceptive effect of amitriptyline, and the ability of caffeine to reverse it, were examined us...
Article
Unlabelled: In the present study, the adrenergic receptor (AR) subtype mediating adrenergic augmentation of P2X(3) receptor-mediated nociceptive responses on sensory nerve endings was examined by using selective AR receptor agonists and antagonists in Sprague Dawley rats in the uninjured state. Local administration of alphabeta-methyleneATP (ligan...
Article
Adenosine and ATP, via P1 and P2 receptors respectively, can modulate pain transmission under physiological, inflammatory, and neuropathic pain conditions. Such influences reflect peripheral and central actions and effects on neurons as well as other cell types. In general, adenosine A1 receptors produce inhibitory effects on pain in a number of pr...
Article
Unlabelled: The present study was undertaken to characterize spontaneous (ie, nonevoked) pain behaviors (flinching, biting/licking) produced by local injections of capsaicin into the rat hindpaw as a model of chemogenic pain, and to determine effects of inflammatory mediators and nerve injury on such behaviors. Capsaicin antagonists are a potentia...
Article
Unlabelled: Twenty eight subjects with refractory, moderate to severe peripheral neuropathic pain participated in an open label prospective trial examining perceived analgesic effect, patient satisfaction, and safety of topical amitriptyline 2%/ketamine 1% cream. Outcome measures included an 11-point numerical rating scale for pain intensity (NRS-...
Article
Local administration of amitriptyline into the rat hindpaw produces peripheral antinociception; this is reduced by adenosine receptor antagonists and appears to involve endogenous adenosine. The present study used peripheral microdialysis: (a) to determine whether amitriptyline could enhance extracellular tissue levels of endogenous adenosine in th...
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A double-blind, randomized, placebo-controlled 3-week study evaluated the efficacy of topical 2% amitriptyline, 1% ketamine, and a combination of both in treating patients with neuropathic pain. Ninety-two patients with diabetic neuropathy, postherpetic neuralgia, or postsurgical/posttraumatic neuropathic pain with allodynia, hyperalgesia, or pinpr...
Article
Neuropathic pain can be difficult to treat clinically, as current therapies involve partial effectiveness and significant adverse effects. Following the development of preclinical models for neuropathic pain, significant advances have been made in understanding the neurobiology of neuropathic pain. This includes an appreciation of the molecular ent...
Article
Peripherally administered amitriptyline exhibits potential to be a locally active analgesic, while ATP augments peripheral nociception by interacting with P2X(3) receptors on sensory afferents. The present study examined the effects of amitriptyline on flinching and biting/licking behaviours and thermal hyperalgesia produced by alphabeta-methylene-...
Article
ATP is implicated in peripheral nociception following activation of P2X, and particularly P2X3 receptors. The present study examined interactions between αβ‐methylene‐ATP (a P2X3 receptor ligand) and 5‐hydroxytryptamine (5‐HT), noradrenaline (NA) and histamine, following local administration into the hindpaw, on spontaneous pain behaviors and therm...
Article
Unlabelled: Opioids increase spinal release of adenosine in rats, and analgesia from systemic and intrathecal morphine is reduced in animals by adenosine receptor antagonists. We performed 3 studies to determine whether opioid administration also induces adenosine release in humans. To determine the effect of intrathecal opioid exposure, 15 women...
Article
Glutamate (which facilitates peripheral nociception) releases adenosine (which inhibits peripheral nociception via adenosine A(1) receptors) when injected locally into the rat hindpaw. The present study determined whether this locally released adenosine could modulate spontaneous pain behaviors produced by a local injection of 1.5% formalin, by det...
Article
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The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of...
Article
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Unlabelled: In this study, we examined antihyperalgesic and analgesic actions after local peripheral administration of ketamine and amitriptyline in a rat model of mild thermal injury. Exposure of the hindpaw to 52 degrees C for 45 s under anesthesia produced a subsequent thermal hyperalgesia lasting at least 2 h. The local peripheral administrati...
Article
Tricyclic antidepressants (TCAs) have been used for chronic pain management for decades; however, their potential use as topical analgesics is an area of new research. The article highlights recent findings relating to the mode of action of TCAs and summarizes results of animal testing of these agents as analgesics. A review of existing and emergin...
Article
Adenosine analogs produce analgesic actions in nociceptive paradigms and alleviate manifestations of neuropathic pain in nerve injury models in rodents. In humans, previous work indicates an analgesic effect for adenosine administered intravenously in postoperative and neuropathic pain. In this double blind placebo controlled crossover trial, we us...
Article
In the central nervous system (CNS), adenosine is an important neuromodulator and regulates neuronal and non-neuronal cellular function (e.g. microglia) by actions on extracellular adenosine A(1), A(2A), A(2B) and A(3) receptors. Extracellular levels of adenosine are regulated by synthesis, metabolism, release and uptake of adenosine. Adenosine als...
Article
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Acute nociceptive, inflammatory, and neuropathic pain all depend to some degree on the peripheral activation of primary sensory afferent neurons. The localized peripheral administration of drugs, such as by topical application, can potentially optimize drug concentrations at the site of origin of the pain, while leading to lower systemic levels and...
Article
The local, peripheral administration of antidepressants and excitatory amino acid receptor antagonists can cause analgesia in a number of conditions. The present study examined the effects of combinations of dextromethorphan and ketamine, two clinically used N-methyl-D-aspartate (NMDA) receptor antagonists, with amitriptyline on formalin-evoked beh...
Article
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The formalin test was introduced as a model of tonic pain in 1977, and has since been used extensively in rats and mice. In rats, formalin generates an initial phase of activity (5–10 min, phase 1), a quiescent interphase (5–10 min), and a second phase of activity (lasting 60–90 min, phase 2), and this is seen with spontaneous behaviors, firing of...
Article
In the central nervous system, adenosine plays an important physiological role in the regulation of neuronal activity and in neuroprotection. Adenosine actions are mediated by cell surface adenosine receptors (A1, A2A, A2B, A3) which are all linked to G-proteins, and activation of these receptors can recruit a number of second messenger systems [1,...
Article
The present study examined the effects of local peripheral and systemic administration of three clinically used excitatory amino acid receptor antagonists (dextromethorphan, memantine, ketamine) on pain behaviors and edema produced by formalin (1.5% and 5%) in rats. Peripheral administration of dextromethorphan produced a locally mediated suppressi...
Article
Unlabelled: We examined the effects of systemically administered gabapentin on flinching and biting/licking behaviors produced by 2.5% formalin in the rat, compared these with those of amitriptyline, and determined the effects of combinations of gabapentin with amitriptyline. Gabapentin produced a dose-related inhibition of Phase 2, but not Phase...
Article
Glutamate receptors have been identified on the peripheral terminals of both primary sensory afferents and sympathetic post-ganglionic neurons, and activation of these receptors produces peripheral sensitization and enhances nociception. Adenosine is an endogenous agent that has a regulatory effect on pain. In brain and spinal cord, adenosine relea...
Article
Unlabelled: We examined the effects of systemically, spinally, and peripherally administered amitriptyline on formalin-induced Fos immunoreactivity in the lumbar spinal cord. Formalin (2.5%), injected subcutaneously into the rat hindpaw, increased Fos immunoreactivity in laminae I-II, III-IV, and V-VI of the dorsal L5 spinal cord. Amitriptyline, a...
Article
Modulation of endogenous adenosine levels by inhibition of adenosine metabolism produces a peripheral antinociceptive effect in a neuropathic pain model. The present study used microdialysis to investigate the neuronal mechanisms modulating extracellular adenosine levels in the rat hind paw following tight ligation of the L5 and L6 spinal nerves. S...
Article
This study was designed to determine (1) whether chronic amitriptyline administration was effective in alleviating symptoms of neuropathic pain in a rat model of spinal nerve injury, and (2) whether the effect of amitriptyline involved manipulation of endogenous adenosine, by determining the effect of caffeine, a non-selective adenosine A(1) and A(...
Article
Injection of formalin into the rat hind paw produces a dose-dependent local peripheral release of adenosine. Low doses of formalin (0.5-2.5%) evoke release during the first 10 min following injection, while a high dose of formalin (5%) evokes release lasting for 60 min. The current study was designed to determine the possible origin of release prod...
Article
The present study (1) examined analgesic effects of systemically and spinally administered antidepressants (ADs) on phase 2 flinching and biting/licking behaviours in the rat formalin test, a model considered to be of greater relevance to clinical pain than acute threshold tests, and (2) determined whether motor or anti-inflammatory effects contrib...
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Although the mechanistic basis of antidepressant action has been actively investigated since their introduction as psy- chotropic agents, a particular focus on mechanisms involved in analgesia is more recent. The mechanisms involved appear to differ — analgesic properties occur independently of antidepressant actions, with a faster onset of action,...
Article
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Antidepressants, given systemically, are widely used for the treatment of various chronic and neuropathic pain conditions in humans. In animal studies, antidepressants exhibit analgesic properties in nociceptive, inflammatory and neuropathic test systems, with outcomes depending on the specific agent, the particular test, the route of administratio...
Article
Background: Spinal or systemic adenosine can alleviate neuropathic pain both in humans and in animal models. Peripheral analgesic effects of adenosine have been demonstrated in rodent inflammatory pain models.Purpose: To examine the effects of local peripheral administration of adenosine agonists and inhibitors of adenosine metabolism in a rat neur...
Article
The present study examined the effects of local subcutaneous administration of formalin on adenosine release from the rat hind paw, and the effects of inhibitors of adenosine metabolism on such release. Microdialysis probes were inserted into the subcutaneous tissue of the plantar surface of rat hind paws. Samples were collected every 10 min at a p...
Article
In the present study, we sought to determine whether administration of caffeine, a non-selective adenosine receptor antagonist, would affect the thermal antihyperalgesic efficacy of acute amitriptyline in a rat model of neuropathic pain. Rats were rendered neuropathic by unilateral tight ligation of the fifth and sixth lumbar spinal nerves, and tes...
Article
Both the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine and the adenosine A(2B/3) receptor agonist N(6)-benzyl-5'-N-ethylcarboxamido adenosine (N(6)-B-NECA) produce an acute paw oedema response following local s.c. injection into the rat hindpaw. This study characterized aspects of the mechanisms by which these responses occur by determi...
Article
The present study used plethysmometry to examine oedema following local injection of selective adenosine A(1), A(2) and A(3) receptor agonists and inhibitors of adenosine metabolism into the hindpaw of the rat. N(6)-Cyclopentyladenosine and L-N(6)-phenylisopropyladenosine (A(1)), 2-[p(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine h...
Chapter
5-Hydroxytryptamine (5-HT) plays a multifaceted role in the regulation of nociceptive transmission. Complexity arises from actions at multiple sites within the pain transmission system (periphery, spinal cord, supraspinal sites), actions at multiple 5-HT receptor subtypes with the potential for opposing or interactive influences, and interactions w...
Article
Spinal administration of an adenosine kinase inhibitor, alone or in combination with an adenosine deaminase inhibitor, produces antinociception in inflammatory pain tests. In the present study, we examined the antinociceptive and anti-inflammatory effects produced by the peripheral (intraplantar) administration of 5'-amino-5'-deoxyadenosine (an ade...
Article
Amitriptyline, a non-selective noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor, has recently been demonstrated to produce a peripheral antinociceptive action in an inflammatory (formalin test) and a neuropathic pain model (spinal nerve ligation). In the present study, we determined whether desipramine, a selective NA reuptake i...
Article
The present study was designed to determine whether amitriptyline, a prototypical tricyclic antidepressant, could produce pain relieving properties in a rat model of neuropathic pain. Nerve injury was produced by tight ligation of the lumbar 5th and 6th dorsal roots and this resulted in persistent stimulus evoked neuropathic pain symptoms (tactile...
Article
The present study determined (1) whether amitriptyline could produce a local antinociceptive action in the formalin test, (2) whether endogenous adenosine was involved in this action, and (3) which other systems might contribute to such an action. Coadministration of amitriptyline 10-100 nmol with 2.5% formalin produced a dose-related reduction in...
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Article
The peripheral administration of adenosine agonists can produce pain inhibitory effects due to adenosine A1 receptor activation, and pain facilitatory effects due to adenosine A2 and A3 receptor activation. Pain facilitatory effects for A2-like receptors result from interactions with endogenous mediators like 5-hydroxytryptamine. Both pain facilita...
Article
Adenosine and ATP exert multiple influences on pain transmission at peripheral and spinal sites. At peripheral nerve terminals in rodents, adenosine A1 receptor activation produces antinociception by decreasing, while adenosine A1 receptor activation produces pronociceptive or pain enhancing properties by increasing, cyclic AMP levels in the sensor...