Search

Phoneutria nigriventer venom (PNV) is a complex mixture of toxins exerting multiple pharmacological effects that ultimately result in severe local pain at the site of the bite. It has been proposed that the PNV-induced pain is mediated by both peripheral and central mechanisms. The nociception triggered by PNV is peripherally mediated by the activation of B 2 , 5-HT 4 , NMDA, AMPA, NK 1 , and NK 2 receptors, as well as TTXS-Na + , ASIC, and TRPV1 channels. The activation of tachykinin, glutamate and CGRP receptors along with the production of inflammatory mediators are, at least partially, responsible for the central component of pain. Despite its well established pro-nociceptive properties, PNV contains some toxins with antinociceptive activity, which have been studied in the last few years. The toxins ω-CNTX-Pn4a, ω-CNTX-Pn2a, ω-CNTX-Pn3a, κ-CNTX-Pn1a, U 7 -CNTX-Pn1a, δ-CNTX-Pn1a, and Γ-CNTX-Pn1a from PNV, as well as the semi-synthetic peptide PnPP-19 have been tested in different experimental models of pain showing consistent antinociceptive properties. This review aims to discuss the pro- and antinociceptive actions of PNV and its toxins, highlighting possible mechanisms involved in these apparently dualistic properties., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The therapeutic potential of snake venoms for pain control has been previously demonstrated. In the present study, the antinociceptive effects of Micrurus lemniscatus venom (MlV) were investigated in experimental models of pain. The antinociceptive activity of MIV was evaluated using the writhing, formalin, and tail flick tests. Mice motor performance was assessed in the rota rod and open field tests. In a screening test for new antinociceptive substances--the writhing test--oral administration of MlV (19.7-1600 μg/kg) produced significant antinociceptive effect. The venom (1600 μg/kg) also inhibited both phases of the formalin test, confirming the antinociceptive activity. The administration of MlV (1600 μg/kg) did not cause motor impairment in the rota rod and open field tests, which excluded possible non-specific muscle relaxant or sedative effects of the venom. The MIV (177-1600 μg/kg) also increases the tail flick latency response, indicating a central antinociceptive effect for the venom. In this test, the MlV-induced antinociceptive effect was long-lasting and higher than that of morphine, an analgesic considered the gold standard. In another set of experiments, the mechanisms involved in the venom-induced antinociception were investigated through the use of pharmacological antagonists. The MlV (1600 μg/kg) antinociceptive effect was prevented by naloxone (5 mg/kg), a non-selective opioid receptor antagonist, suggesting that this effect is mediated by activation of opioid receptors. In addition, the pre-treatment with the μ-opioid receptor antagonist CTOP (1 mg/kg) blocked the venom antinociceptive effect, while the k-opioid receptor antagonist nor-BNI (0.5 mg/kg) or the δ-opioid receptor antagonist naltrindole (3 mg/kg) only partially reduced the venom-induced antinociception. The present study demonstrates, for the first time, that oral administration of M. lemniscatus venom, at doses that did not induce any motor performance alteration, produced potent and long-lasting antinociceptive effect mediated by activation of opioid receptors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The anterior pretectal nucleus (APtN) participates in nociceptive process and controls spinal nociceptive inputs, and its integrity reduces the severity of the responses to persistent injury. In this study we examined whether the pedunculopontine tegmental nucleus (PPTg) or the gigantocellularis nucleus pars alpha (GiA), stations that relay APtN inputs to the spinal cord, can control the persistent pain induced by a hind paw incision in rats with disrupted APtN. The withdrawal threshold to mechanical stimulation of the incised paw measured with von Frey filaments was significantly reduced in rats with contralateral APtN lesion or neural block of this nucleus with 2% lidocaine. Intrathecal xylamine, an inhibitor of noradrenaline uptake, inhibited the neural block of the APtN-induced increase in the incisional pain. Injection of glutamate into the contralateral PPTg or ipsilateral GiA reduced the incisional pain. Neural block of the PPTg or GiA reduced the threshold, mainly in APtN-disrupted rats. We conclude that persistent noxious stimulation activates descending pathways involving the contralateral APtN and PPTg, and ipsilateral GiA. Disruption of the APtN allows the activation of alternative circuitry involving at least the PPTg and GiA as intermediary stations that might maintain the control of nociceptive inputs in the spinal cord, probably involving noradrenergic mechanisms.