Melittin selectively activates capsaicin-sensitive primary afferent fibers

Abstract

Whole bee venom (WBV)-induced pain model has been reported to be very useful for the study of pain. However, the major constituent responsible for the production of pain by WBV is not apparent. Intraplantar injection of WBV and melittin dramatically reduced mechanical threshold, and increased flinchings and paw thickness. In behavioral experiments, capsaicin pretreatment almost completely prevented WBV- and melittin-induced reduction of mechanical threshold and flinchings. Intraplantar injection of melittin increased discharge rate of dorsal horn neurons only with C fiber input from peripheral receptive field, which was completely blocked by topical application of capsaicin to sciatic nerve. These results suggest that both melittin and WBV induce nociceptive responses by selective activation of capsaicin-sensitive afferent fibers.

Spinal Metabotropic Glutamate Receptors (mGluRs) are Involved in the Melittin-induced Nociception in Rats

“…Intrathecal administration of group I mGluR antagonist has been suggested to block C-fiber-induced spinal nociceptive responses, and this suggestion is consistent with the observation that melittin selectively activates primary afferent C-fibers (Shin & Kim, 2004) and that melittin-induced nociceptive responses were suppressed by i.t. group I mGluR antagonist in the present study.…”

“…injection of melittin have the same characteristics as those of bee venom-induced pain . Melittin has been shown to induce nociceptive responses by selective activation of capsaicin-sensitive primary afferent fibers (Shin & Kim, 2004). Melittin-induced nociceptive responses have been reported to be moduated by changes in the activities of voltage-sensitive Ca 2+ channels , multiple 5-hydroxytryptamine receptors (Shin & Lee, 2007), cyclooxygenase (Kim et al, 2006), extracellular signaling-regulated kinase (Yu & Chen, 2005), NMDA and non-NMDA receptors (Kim & Shin, 2005).…”

The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword

“…1, Table 1), a strongly basic 26 amino-acid polypeptide which constitutes 40–60% of the whole dry honeybee venom, has various biological, pharmacological and toxicological actions including strong surface activity on cell lipid membranes, hemolyzing activity, antibacterial and antifungal activities (Habermann, 1972, 1974; Gauldie et al, 1976; Lariviere and Melzack, 1996) and antitumor properties (Orsolic et al, 2003; Liu et al, 2008a,b). Recently, melittin has also been demonstrated to cause neural plastic changes along pain-signaling pathways by activation and sensitization of nociceptor cells via phosphorylation of mitogen-activated protein kinases (MAPK) (Hao et al, 2008; Yu et al, 2009), activations of thermal nociceptive channels (transient receptor potential vanilloid receptor 1, TRPV1) (Li and Chen, 2004; Shin and Kim, 2004; Chen et al, 2006a,b) and ATP P2X and P2Y receptors (Lu et al, 2008). Contrarily, melittin has also been believed to be the major biologically active substance of bee venom to play a role in production of anti-nociceptive and anti-inflammatory effects when applied to the acupoint of a subject (‘apipuncture’) (Son et al, 2007).…”

The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

“…Among these components, melittin is likely to play the most important role in the production of pain, hyperalgesia, allodynia, and inflammatory process [29]. Melittin has been reported to selectively activate capsaicin-sensitive primary afferent fibers [30] and small- to medium-sized DRG cells by opening the nonselective transient receptor potential vanilloid 1 (TRPV1) cation ion channel [31]. Either pre- or posttreatment with capsazepine, a selective blocker of thermal nociceptor TRPV1, significantly prevents or suppresses the persistent, spontaneous nociception induced by intraplantar injection of melittin [29].…”