Pivotal role of capsaicin-sensitive primary afferents in development of both heat and mechanical hyperalgesia induced by intraplantar bee venom injection.

To investigate the roles of primary afferent fibers in development of the bee venom (BV)-induced persistent spontaneous nociception (PSN) and hyperalgesia (HA), the sciatic nerve or both the sciatic and saphenous nerves of rats were topically treated with capsaicin respectively under pentobarbital anesthesia to destroy the capsaicin-sensitive primary afferent (CSPA) fibers. Effect of the sciatic nerve capsaicin on the formalin-induced PSN was also evaluated. Destruction of the CSPA fibers of the sciatic nerve or both the sciatic and saphenous nerves only produced 34 or 69% inhibition of the mean total number of 1 h BV-induced paw flinches. However, the total number of 1 h formalin-induced paw flinches was inhibited by 90% (85% for phase 1 and 91% for phase 2). In naïve rats, destruction of the CSPA fibers of the sciatic nerve caused 237 and 60% increase in paw withdrawal thermal latency (PWTL) to radiant heat in the injection site (paw pad) and at the heel of the treated hind paw compared to the baseline values. However, it was without significant influence upon the PWTL in the non-treated side or the paw withdrawal mechanical threshold (PWMT) to von Frey filament stimuli in both hind paws. In the BV-treated rats, the CSPA fiber destruction of the sciatic nerve completely blocked development of the heat and mechanical HA in the BV injection site. However, the reduction in either PWTL (drop to baseline level) or PWMT (drop by 56% from the baseline level) at the heel of the BV-treated side was not affected by this treatment. However, destruction of the CSPA fibers of both the sciatic and saphenous nerves was able to block development of both heat and mechanical HA in the whole BV-treated hind paw and heat hyperalgesia in the non-injected hind paw. Taken together, we conclude that: (1) the CSPA (C- and A delta-) fibers play a pivotal role in mediation of either the heat or the mechanical hyperalgesia induced by s.c. BV; (2) the CSPA fibers may play a crucial role in mediation of the formalin-induced PSN, but play a partial role in the BV-induced nociceptive process; (3) in addition to the sciatic nerve, the saphenous nerve is also involved in mediation of the BV-induced PSN as well as heat and mechanical hyperalgesia, while it is not likely to be involved in the formalin-induced nociception.