Antiallodynic effect and side effects of Ph alpha 1 beta, a neurotoxin from the spider Phoneutria nigriventer: Comparison with omega-conotoxin MVIIA and morphine

作者：de Souza A H; Lima M C; Drewes C C; da Silva J F; Torres K C L; Pereira E M R; de Castro Junior C J; Vieira L B; Cordeiro M N; Richardson M; Gomez R S; Romano Silva M A; Ferreira J; Gomez M V^*

来源：Toxicon, 2011, 58(8): 626-633.

DOI：10.1016/j.toxicon.2011.09.008

• Incisional pain
• Antiallodynic effect
• Adverse effects
• Toxins
• Morphine
• Ca(2+) channels

Ph alpha 1 beta is a potent toxin obtained from the spider Phoneutria nigriventer that blocks neuronal voltage-sensitive Ca(2+) channels. This study compared the antiallodynic effects of Ph alpha 1 beta, omega-conotoxin MVIIA and morphine in mice and their side effects in rats. Mechanical allodynia was measured in mice receiving single intrathecal administration of Ph alpha 1 beta, omega-conotoxin MVIIA or morphine before or after the incisional plantar procedure. The effect of the treatments on cardiovascular profile and global neurological were evaluated in rats. The expression of pro or anti-inflammatory cytokines of human polymorph mononuclear cells was also evaluated. Preemptive use of omega-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site) induced shorter antiallodynic effect than Ph alpha 1 beta (100 pmol/site) in mice. Post-incision administration of Ph alpha 1 beta (200 pmol/site) induced longer mechanical antiallodynic effect than omega-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site). Intrathecal injection of Ph alpha 1 beta (200 pmol/site) and morphine (433 pmol/site) did not change while omega-conotoxin MVIIA (100 pmol/site) increased the heart rate in rats 3 h after its administration. Ph alpha 1 beta (200 pmol/site), omega-conotoxin MVIIA (100 pmol/site) and morphine (433 pmol/site) did not change mean arterial pressure 0.5 and 3 h after their administration. The treatments did not alter neurological performance assessed by global neurological evaluation and open-field test. The tested drugs did not induced expression of pro or anti-inflammatory cytokines in CD4 monocytes. In conclusion, preemptive administration Ph alpha 1 beta in mice induced longer antiallodynic effect than omega-conotoxin MVIIA and morphine. Ph alpha 1 beta also induced a longer mechanical antiallodynic effect than omega-conotoxin MVIIA and morphine when used after the surgical incision. The present results suggest that Ph alpha 1 beta has a potential application in the management of postoperative pain with low side effects. Published by Elsevier Ltd.

• 出版日期2011-12-1