title: The analgesic effect of crotoxin on neuropathic pain is mediated by central muscarinic receptors and 5-lipoxygenase-derived mediators.
abstract: Crotoxin (CTX), a neurotoxin isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, induces analgesia. In this study, we evaluated the antinociceptive effect of CTX in a model of neuropathic pain induced by rat sciatic nerve transection. Hyperalgesia was detected 2 h after nerve transection and persisted for 64 days. Immersion of proximal and distal nerve stumps in CTX solution (0.01 mM for 10 s), immediately after nerve transection, blocked hyperalgesia. The antinociceptive effect of CTX was long-lasting, since it was detected 2 h after treatment and persisted for 64 days. CTX also delayed, but did not block, neurectomy-induced neuroma formation. The effect of CTX was blocked by zileuton (100 mg/kg, p.o.) and atropine (10 mg/kg, i.p.), and reduced by yohimbine (2 mg/kg, i.p.) and methysergide (5 mg/kg, i.p.). On the other hand, indomethacin (4 mg/kg, i.v.), naloxone (1 mg/kg, i.p.), and N-methyl atropine (30 mg/kg, i.p.) did not interfere with the effect of CTX. These results indicate that CTX induces a long-lasting antinociceptive effect in neuropathic pain, which is mediated by activation of central muscarinic receptors and partially, by activation of alpha-adrenoceptors and 5-HT receptors. Eicosanoids derived from the lipoxygenase pathway modulate the action of crotoxin.
authors.affiliation: Laboratory of Pathophysiology, Butantan Institute, Vital Brazil Av., 1500, 05503-900, Sao Paulo, SP, Brazil.
authors.forename: Francisco de Sousa
authors.initials: Fde S
authors.lastname: Nogueira-Neto
authors.forename: Renée L
authors.initials: RL
authors.lastname: Amorim
authors.forename: Patrícia
authors.initials: P
authors.lastname: Brigatte
authors.forename: Gisele
authors.initials: G
authors.lastname: Picolo
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Ferreira
authors.forename: Vanessa P
authors.initials: VP
authors.lastname: Gutierrez
authors.forename: Isaltino Marcelo
authors.initials: IM
authors.lastname: Conceição
authors.forename: Maisa S
authors.initials: MS
authors.lastname: Della-Casa
authors.forename: Regina K
authors.initials: RK
authors.lastname: Takahira
authors.forename: José Luis M
authors.initials: JL
authors.lastname: Nicoletti
authors.forename: Yara
authors.initials: Y
authors.lastname: Cury
mesh_terms: D018712:Analgesics, Non-Narcotic; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism / Q000502:physiology*; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D003439:Crotoxin / Q000494:pharmacology*; D015777:Eicosanoids / Q000378:metabolism / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy / Q000523:psychology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012584:Sciatic Nerve / Q000293:injuries; D012701:Serotonin / Q000502:physiology
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D011976:Receptors, Muscarinic; D012701:Serotonin; D009270:Naloxone; D003439:Crotoxin; D001094:Arachidonate 5-Lipoxygenase; D003402:Creatine Kinase; D007213:Indomethacin