Cytokines are involved with the development and maintenance of inflammatory and neuropathic pain. These molecules, which can be released from numerous cell types including leukocytes and endothelial cells, exert their effects directly or indirectly on nerve terminals located in the periphery, on neurons of sensory ganglia and on nociceptive sensing neurons in the spinal cord. To better understand the mechanism by which these molecules influence nociception at the level of the sensory ganglia, we treated embryonically cultured DRG neurons with the pro-nociceptive cytokines TNF-&Alpha, monocyte chemoattractant protein-1 (MCP-1/CCL2) or macrophage inflammatory protein-1&Alpha (MIP-1&Alpha/CCL3) and examined the expression of numerous genes involved in nociceptive processing after 2 or 24 h. Among the genes induced by TNF-&Alpha are cox-2, interleukin-1&Beta, S100A8 and CCL2. TNF-&Alpha-induced CCL2 upregulation is also associated with a release of MCP-1/CCL2 into the medium, as determined by ELISA. Treatment with MCP-1/CCL2 induced fewer genes than TNF-&Alpha, but it dramatically induced CCL2 in neurons as determined by RT-PCR and in situ hybridization. In contrast to TNF-&Alpha and MCP-1/CCL2, MIP-1&Alpha/CCL3 did not induce the expression of any of the genes tested (including CCL3). Moreover, CCL3 was not induced by TNF-&Alpha or MCP-1/CCL2. Thus data from these experiments suggests mechanisms by which these cytokines contribute to pain and highlight cytokines that may be involved in the maintenance of chronic pain at the level of the sensory ganglia. Importantly, hind paw administration of TNF-&Alpha, MCP-1/CCL2 or MIP-1&Alpha/CCL3 has been reported to induce hyperalgesia in rats. We are currently investigating whether this hyperalgesic response is associated with an increase in genes involved in nociceptive processing in the sensory ganglia.