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Crotalphine, a 14 amino acid peptide first isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, induces a peripheral long-lasting and opioid receptor-mediated antinociceptive effect in a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. In the present study, we further characterized the molecular mechanisms involved in this effect, determining the type of opioid receptor responsible for this effect and the involvement of the nitric oxide–cyclic GMP pathway and of Kchannels. Crotalphine (0.2 or 5 gkg, orally; 0.0006 gpaw), administered on day 14 after nerve constriction, inhibited mechanical hyperalgesia and low-threshold mechanical allodynia. The effect of the peptide was antagonized by intraplantar administration of naltrindole, an antagonist of -opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of -opioid receptors. The effect of crotalphine was also blocked by 7-nitroindazole, an inhibitor of the neuronal nitric oxide synthase; by 1H-(1,2,4) oxadiazolo4,3-aquinoxaline-1-one, an inhibitor of guanylate cyclase activation; and by glibenclamide, an ATP-sensitive Kchannel blocker. The results suggest that peripheral -opioid and -opioid receptors, the nitric oxide–cyclic GMP pathway, and ATP-sensitive Kchannels are involved in the antinociceptive effect of crotalphine. The present data point to the therapeutic potential of this peptide for the treatment of chronic neuropathic pain.

A new acylamino acid, bunodosine 391 (BDS 391), was isolated from the venom of the sea anemone Bunodosoma cangicum. The structure was elucidated by spectroscopic analyses (2D NMR, ESIMS/MS) and verified by its synthesis. Intraplantar injection of BDS 391 into the hind paw of a rat induced a potent analgesic effect. This effect was not altered by naloxone (an opioid receptor antagonist), but was completely reversed by methysergide (a serotonin receptor antagonist), indicating that the effect is mediated by activation of serotonin receptors.

The capacity to respond to inflammatory stimuli was tested in hyperthyroid and hypothyroid rats when thyroid defects, induced by hormone administration or thyroparathyroidectomy, respectively, were fully established. Whereas hyperthyroid rats presented consistently depressed inflammatory responses, hypothyroid rats responded in a normal fashion. Decreased reactions to intracutaneously injected histamine and serotonin, inhibited swelling reaction to carrageenin, injected into one of the hind paws, and depressed primary and secondary reactions to adjuvant (heat-killedM. tuberculosis), only occurred in the hyperthyroid group. In addition, only in this group of animals enlargement of the adrenal glands, reduced content of adrenal ascorbic acid, and decreased number of circulating eosinophils, which characterize a circumstance of adrenal cortical hyperactivity, were observed. A spontaneous reversal of the acute inflammatory response of hyperthyroid animals to carrageenin occurred 3–4 days after interruption of hormone administration, and this was coincidental with the return to normal of the previously enlarged adrenal glands. Similarly, specific inhibition of adrenal cortical steroid biosynthesis in hyperthyroid rats with amino-glutethimide, restored the previously depressed response to carrageenin, without interference with the increased levels of seric thyroxin, thus suggesting that the inhibitory effects of thyroid hormones on inflammatory responses are likely to be indirect. It is concluded that an excess of circulating thyroid hormones, but not their deficiency, can impair the development of inflammatory reactions, and that this effect, at least partially, depends on an increased secretion of adrenal corticosteroids.

Pain sensitivity can be modulated by an enzyme that degrades aldehydes in rodents, pointing to a promising therapeutic target.

Ctenus medius Keyserling, 1891 (Araneae: Ctenidae) co-occurs in various microhabitats of the Brazilian Atlantic Forest and can be easily misidentified as the medically important spider Phoneutria nigriventer Keyserling, 1981 (Ctenidae). Despite being phylogenetically close to Phoneutria, no data are available about the toxic potential of Ctenus medius venom. Here we show that, although presenting different profile of protein composition, C. medius venom displays some of the toxic properties exhibited by P. nigriventer venom, including proteolytic, hyaluronidasic and phospholipasic activities, as well as the ability of causing hyperalgesia and edema. Moreover, C. medius venom interferes in the activation of the complement system in concentrations that P. nigriventer venom is inactive. Thus, these data show that venoms of spiders from Ctenidae family share important proinflammatory properties and suggest that the C. medius bite may have an important noxious effect in human accidents.