Effects of intravenous administration of recombinant Phα1ß toxin in a mouse model of fibromyalgia.

This study investigated the effects of intravenous (iv) administration of recombinant Phα1ß toxin, pregabalin, and diclofenac by the intrathecal route using an animal model fibromyalgia (FM). The reserpine administration (0.25 mg/kg s. c) once daily for three consecutive days significantly induced hyperalgesia, immobility time, and sucrose consumption in mice on the 4th day. Reserpine caused hyperalgesia on the mechanical and thermal hyperalgesia on the 4th day was reverted by recombinant Phα1ß (0.2 mg/kg iv) and pregabalin (1.25 µmol/site i. t) treatments. In contrast, diclofenac (215 nmol/site i. t) was ineffective. Recombinant Phα1ß toxin, pregabalin, and diclofenac did not affect the depressive-like behavioural effect induced by reserpine on mice during the forced swim and sucrose consumption tests. The data confirmed the analgesic effect of the recombinant Phα1ß toxin administered intravenously in a fibromyalgia mouse model.

Synergistic antinociceptive effect of a calcium channel blocker and a TRPV1 blocker in an acute pain model in mice.

AIMS: Extensive evidence supports a role for voltage-gated calcium channels (VGCC) and TRPV1 receptors in pain transmission and modulation. We investigated the profile of analgesic interaction between Phα1ß toxin (a VGCC blocker) and SB366791 (selective TRPV1 antagonist) in a model of acute pain induced by capsaicin. Changes in body temperature induced by combination regimens were also evaluated. MAIN METHODS: Isobolographic approach with a fixed dose-ratio of combined drugs was used to determine whether antinociceptive interaction of Phα1ß and SB366791 are subadditive, additive or synergic. Body temperature was obtained by thermal infrared imaging. KEY FINDINGS: Phα1ß and SB366791 interact in a synergistic manner to cause antinociception. We found an interaction index (α) of 0.07 for Phα1ß and SB366791 when these drugs were injected together intraplantarly, which indicates that in vivo interaction between these drugs is greater than additive interaction. Synergism also occurred when intraplantar SB366791 was administered simultaneously with intrathecal Phα1ß (interaction index α=0.06) suggesting a 15 fold rise in potency on the analgesic effect of these drugs when they are added together. It was observed no significant alterations in body temperature of animals treated with this combination regimen. SIGNIFICANCE: Our data reveal that Phα1ß toxin potentiates in 15 fold the antinociceptive action of the TRPV1 blocker SB366791. Therefore, lower doses of these drugs are required to achieve antinociceptive effects when these agents are given in combination.