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

Abstract

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.

Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

“…Similarly, the anti-arthritic activity of Indian monocellate cobra venom was also verified [5]. We have previously reported that cobratoxin (CTX), the long-chain α -neurotoxin from Thailand cobra venom, had anti-inflammatory and antinociceptive effects on adjuvant arthritis [6] and can relieve the formalin-induced inflammatory pain in rats [7]. Naja Naja atra (Chinese cobra) and itstoxic components were considered as a medicine in traditionalChinese medicine.…”

The Protective Effects of Cobra Venom fromNaja naja atraon Acute and Chronic Nephropathy

“…Among them, CVF depletes compliment C3 and thus inhibits inflammatory and immune responses [13]. Our recent study also revealed that neurotoxin in cobra venom inhibited inflammatory response [14]. Previous studies have shown that snake venoms have beneficial effects on the treatment of various pathophysiological conditions, including Parkinson's diseases [15], ischemia [16], and pain [14].…”

“…Our recent study also revealed that neurotoxin in cobra venom inhibited inflammatory response [14]. Previous studies have shown that snake venoms have beneficial effects on the treatment of various pathophysiological conditions, including Parkinson's diseases [15], ischemia [16], and pain [14]. Peptide neurotoxins from snake venoms were used for the identification and characterization of membrane ion channels and receptors in human neurons [17].…”

Cobra neurotoxin produces central analgesic and hyperalgesic actions via adenosine A1 and A2A receptors

“… 7 , 8 CNT is generally regarded as an antagonist to cholinergic receptors due to its inhibition on inflammatory pain weakened by nicotinic acetylcholine receptors antagonist. 9 However, recently it has been reported that CNT causes trigeminal neuralgia at higher dose, 10 which is contrary to such a mechanism. CNT, like other toxin, 11 may exhibit dual pain regulation, with analgesia and hyperalgesia in different physiological conditions or dosage through interaction with different receptors and signal pathways.…”