A long-form alpha-neurotoxin from cobra venom produces potent opioid-independent analgesia1

Chen, Zhuo; Zhang, Huiling; Z, Gu; Chen, Bowen; Han, Rong; Reid, Paul F.; Raymond, Laurence N; Qin, Zheng‐Hong

doi:10.1111/j.1745-7254.2006.00293.x

Cited by 63 publications

(49 citation statements)

References 21 publications

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“…Cholinergic signals derived from vagus nerve stimulation inhibit the release of TNF, IL-1, HMGB1, and other cytokines by transducing cellular signals that inhibit the nuclear activity of NF-κB [38] . In contrast to the roles of nicotinic cholinergic receptors agonists discussed earlier, the present study indicates that CTX, which may be a nicotinic antagonist, also has a role in inflammatory relief [19,39] . As far as we know, no reports demonstrate that CTX interacts with any receptor other than AChR.…”

Section: Discussioncontrasting

confidence: 99%

“…The analgesic effects of CTX were antagonized by atropine, but not naloxone. These results indicated that CTX produced potent opioid-independent analgesia [19] . Recently, we also found that CTX exhibited a dose-dependent analgesic action in formalin-induced phase 1 and phase 2 pain responses and inhibited enhancement of c-Fos-positive cells in the spinal cord (Liu et al, manuscript submitted).…”

Section: Introductionmentioning

confidence: 82%

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Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

et al. 2009

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Aim: Cobratoxin (CTX), the long-chain α-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models. The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adjuvant arthritis (AA) in rats. Methods: Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration. Tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA. Histopathological changes in synoviocytes were examined under a microscope. Involvement of the cholinergic system in the effects of CTX was examined by pretreatment of animals with the α 7 nicotinic receptor (α 7 -nAChR) antagonist methyllycaconitine (MLA). Results: CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-α, IL-1 and IL-2 in the serum of AA rats were increased, whereas the level of IL-10 was decreased. Histopathological examination of synoviocytes showed pronounced inflammation and accumulation of collagen. The administration of CTX (17.0 µg/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-α, IL-1, and IL-2 but increased the production of IL-10 and altered pathohistological changes. The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg, sc). Conclusion: These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines. α 7 -nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 82%

Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

et al. 2009

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“…Of the neurotoxins, the α-neurotoxins competitively bind to the postsynaptic neuronal and skeletal muscular nicotinic cholinergic receptors (nAChRs), leading to muscular paralysis (10). There is also evidence to show that some of the α-neurotoxins result in a centrally mediated opiate-independent analgesia through the nAChRs and can substitute morphine and mitigate opioid withdrawal (7,11). Given the role of nAChRs in rewarding or euphoric experiences associated with substance use mediated through the mesolimbic dopaminergic system, it seems plausible to assume that the pleasurable experiences described by our patients may be mediated by the same pathway (12).…”

Section: Discussionmentioning

confidence: 99%

Snake Bite as a Novel Form of Substance Abuse: Personality Profiles and Cultural Perspectives

et al. 2011

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“…The peak effect of analgesia was seen 3 h after CTX administration. Furthermore, naloxone failed to block the analgesic effects of CTX, but atropine did antagonize the analgesia mediated by CTX in the mouse acetic acid writhing test, indicating that the cholinergic, but not opioid system, appears to be involved in the antinociceptive action of CTX [8] . It is not currently known whether CTX inhibits inflammatory pain.…”

Section: Introductionmentioning

confidence: 90%

Involvement of cholinergic system in suppression of formalin-induced inflammatory pain by cobratoxin

Shi

Hua

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the analgesic effect of cobratoxin (CTX), a long-chain α-neurotoxin from Thailand cobra venom, in a rat model of formalin-induced inflammatory pain. Methods: Inflammatory pain was induced in SD rats via injecting 5% formalin (50 μL) into the plantar surface of their right hind paw. CTX and other agents were ip administered before formalin injection. The time that the animals spent for licking the injected paw was counted every 5 min for 1 h. Results: CTX (25, 34, and 45 μg/kg) exhibited a dose-dependent analgesic effect during the phase 1 (0-15 min) and phase 2 (20-60 min) response induced by formalin. Pretreatment with naloxone (0.5 or 2.5 mg/kg) did not block the analgesic effect of CTX. Pretreatment with atropine at 5 mg/kg, but not at 2.5 mg/kg, antagonized the analgesic effect of CTX. Treatment with the nonselective nAChR antagonist mecamylamine (3 mg/kg) inhibited the analgesic effects of CTX in Phase 1 and Phase 2 responses, while with the selective α7-nAChR antagonist methyllycaconitine (3 mg/kg) antagonized the effect of CTX only in the Phase 1 response. Treatment with the α7-nAChR agonist PNU282987 (3 mg/kg) significantly reduced the formalin-induced phase 2 pain response, but only slightly reduced the Phase 1 pain response. Conclusion:The results suggest that CTX exerts an antinociceptive effect in formalin-induced inflammatory pain, which appears to be mediated by mAChR and α7-nAChR.

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A long-form alpha-neurotoxin from cobra venom produces potent opioid-independent analgesia1

Cited by 63 publications

References 21 publications

Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

Snake Bite as a Novel Form of Substance Abuse: Personality Profiles and Cultural Perspectives

Involvement of cholinergic system in suppression of formalin-induced inflammatory pain by cobratoxin

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