RESUMO
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.
Assuntos
Analgésicos não Narcóticos , Araquidonato 5-Lipoxigenase/fisiologia , Crotoxina/farmacologia , Dor/tratamento farmacológico , Dor/etiologia , Doenças do Sistema Nervoso Periférico/complicações , Receptores Muscarínicos/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Araquidonato 5-Lipoxigenase/metabolismo , Creatina Quinase/sangue , Creatina Quinase/metabolismo , Eicosanoides/metabolismo , Eicosanoides/fisiologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/psicologia , Indometacina/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Limiar da Dor/efeitos dos fármacos , Ratos , Nervo Isquiático/lesões , Serotonina/fisiologiaRESUMO
OBJECTIVE: To evaluate the effects of extracorporeal shock wave therapy (ESWT) on affected ligaments in the hind limbs of horses with experimentally induced suspensory ligament desmitis by use of ultrasonographic, ultrastructural, and immunocytochemical techniques. ANIMALS: 10 horses. PROCEDURE: Suspensory ligament desmitis was induced in both hind limbs of each horse by use of 2 collagenase injections (administered 2 weeks apart) in each suspensory ligament. Two weeks after the second injection, the right hind limb of each horse was treated with ESWT (3 treatments at 3-week intervals); the left hind limb was not treated (control limb). Periodically during the study, the healing process was monitored ultrasonographically and the proportions of ligaments affected with lesions were assessed. Four weeks after the last ESWT treatment, biopsy specimens were collected from all ligaments for ultrastructural evaluation and immunocytochemical analysis of transforming growth factor beta-1. RESULTS: The difference in the proportion of the lesion-affected ligament between ESWT-treated and control limbs was significant (P < 0.05) from 3 weeks after the second ESWT treatment to the end of the study. Compared with control ligaments, ESWT-treated ligaments had more small, newly formed collagen fibrils and greater expression of transforming growth factor beta-1 4 weeks after the last ESWT treatment was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results have indicated that ESWT appears to facilitate the healing process in horses with experimentally induced hind limb suspensory ligament desmitis.