Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain

Żychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Luvisetto, Siro; Pavone, Flaminia; Przewłocka, Barbara; Mika, Joanna

doi:10.1016/j.ejphar.2016.09.019

Cited by 63 publications

(56 citation statements)

References 74 publications

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“…Indeed, whereas Maves et al 50. placed ligatures sliding along the nerve, with no constriction, the ligatures’ tightness that is achieved following the original constriction procedure of Bennett and Xie29 has been regularly reported to produce strong mechanical hyperalgesia not only with chromic gut but also with silk thread around the nerve (see refs 51, 52, 53, 54). Accordingly, marked supersensitivity to mechanical stimulation of ipsilateral hindpaw was also observed after silk thread ligation of the sciatic nerve in CCI-SN rats used in the present study (Figs 3 and 4).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

Jeanson

Duchêne

Richard

et al. 2016

Sci Rep

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Antidepressants, prescribed as first line treatment of neuropathic pain, have a limited efficacy and poorly tolerated side effects. Because recent studies pointed out the implication of astroglial connexins (Cx) in both neuropathic pain and antidepressive treatment, we investigated whether their blockade by mefloquine could modulate the action of the tricyclic antidepressant amitriptyline. Using primary cultures, we found that both mefloquine and amitriptyline inhibited Cx43-containing gap junctions, and that the drug combination acted synergically. We then investigated whether mefloquine could enhance amitriptyline efficacy in a preclinical model of neuropathic pain. Sprague-Dawley rats that underwent chronic unilateral constriction injury (CCI) to the sciatic nerve (SN) were treated with either amitriptyline, mefloquine or the combination of both drugs. Whereas acute treatments were ineffective, chronic administration of amitriptyline reduced CCI-SN-induced hyperalgesia-like behavior, and this effect was markedly enhanced by co-administration of mefloquine, which was inactive on its own. No pharmacokinetic interactions between both drugs were observed and CCI-SN-induced neuroinflammatory and glial activation markers remained unaffected by these treatments in dorsal root ganglia and spinal cord. Mechanisms downstream of CCI-SN-induced neuroinflammation and glial activation might therefore be targeted. Connexin inhibition in astroglia could represent a promising approach towards improving neuropathic pain therapy by antidepressants.

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Section: Discussionmentioning

confidence: 99%

Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

Jeanson

Duchêne

Richard

et al. 2016

Sci Rep

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“…Moreover, recently, in a rat model of neuropathic pain, BoNT/A was shown to influence microglial activation and to restore neuroimmune balance by reducing the levels of pronociceptive factors (IL-1 β and IL-18). In addition, it appears to increase the level of antinociceptive factors (IL-10 and IL-1RA) in the spinal cord and in the dorsal root ganglia (Zychowska et al, 2016). These findings suggest that neuroimmunological changes are also involved in BoNT/A-mediated analgesia.…”

Section: Pharmacologymentioning

confidence: 99%

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

et al. 2017

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The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.

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“…BoNT has been shown to attenuate pain via modification of neuroinflammatory activity induced by nerve damage [113]. In a rat model of neuropathic pain, botulinum toxin administration reduced pain-related behaviors, with corresponding downregulation of pro-inflammatory cytokines (IL-1β and IL-18) and upregulation of anti-inflammatory cytokines (IL-10 and IL-1 receptor antagonist) [114]. The largest trial of BoNT for neuropathic pain is an unpublished study from Allergan (manufacturer of Botox ® ), which found a lack of efficacy of Botox ® for the treatment of postherpetic neuralgia [115].…”

Section: Alternative Approaches To Reduce Neuroinflammmationmentioning

confidence: 99%

Targeting cytokines for treatment of neuropathic pain

Hung

Lim

Doshi

2017

Scandinavian Journal of Pain

140

120

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AbstractBackgroundNeuropathic pain is a challenging condition often refractory to existing therapies. An increasing number of studies have indicated that the immune system plays a crucial role in the mediation of neuropathic pain. Exploration of the various functions of individual cytokines in neuropathic pain will provide greater insight into the mechanisms of neuropathic pain and suggest potential opportunities to expand the repertoire of treatment options.MethodsA literature review was performed to assess the role of pro-inflammatory and antiinflammatory cytokines in the development of neuropathic pain. Both direct and indirect therapeutic approaches that target various cytokines for pain were reviewed. The current understanding based on preclinical and clinical studies is summarized.Results and conclusionsIn both human and animal studies, neuropathic pain has been associated with a pro-inflammatory state. Analgesic therapies involving direct manipulation of various cytokines and indirect methods to alter the balance of the immune system have been explored, although there have been few large-scale clinical trials evaluating the efficacy of immune modulators in the treatment of neuropathic pain. TNF-α is perhaps the widely studied pro-inflammatory cytokine in the context of neuropathic pain, but other pro-inflammatory (IL-1β, IL-6, and IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β) signaling molecules are garnering increased interest. With better appreciation and understanding of the interaction between the immune system and neuropathic pain, novel therapies may be developed to target this condition.

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Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain

Cited by 63 publications

References 74 publications

Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

Targeting cytokines for treatment of neuropathic pain

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