The Pain of Inflammation

Abstract

The advantage of feeling pain is that an organism is alerted to harmful stimuli and encouraged to avoid further exposure. Thus, it makes sense that response to inflammatory signals might be most effective if coupled with a sensitization of the pain circuitry. Zhang et al. provide a mechanism by which such responses may be coupled. They show that the receptor chemokine (C-C motif) receptor 1 (CCR1), which binds chemokines CCL3, CCL5, and CCL7, can be detected on pain-sensing neurons in rat dorsal root ganglia (DRGs) by immunohistochemistry or reverse transcription polymerase chain reaction. The pain-sensing cells respond through a cation channel called the TRPV1 (for transient receptor potential vanilloid 1). Treatment of cultured DRG cells with CCL3 enhanced the response of TRPV1 to a pain stimulus induced by exposure of the cells to capsaicin, the chemical that generates the "heat" in hot peppers. G protein (heterotrimeric guanine nucleotide-binding protein)-dependent signaling from CCR1 to activate phospholipase C and protein kinase C was required to sensitize TRPV1. Chemokines have previously been shown to desensitize receptors on neurons in the central nervous system that respond to pain-relieving opioids. The authors suggest that the two mechanisms may combine to increase the perception of pain during inflammation. N. Zhang, S. Inan, A. Cowan, R. Sun, J. M. Wang, T. J. Rogers, M. Caterina, J. J. Oppenheim, A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1. Proc. Natl. Acad. Sci. U.S.A. 12 , 4536-4541 (2005). [Abstract] [Full Text]