Microarray analysis of rat sensory ganglia after local inflammation implicates novel cytokines in pain.

Abstract

Inflammation plays a role in neuropathic pain conditions as well as in pain induced solely by an inflammatory stimulus. Robust mechanical hyperalgesia and allodynia can be induced by locally inflaming the L5 dorsal root ganglion (DRG) in rat. This model allows investigation of the contribution of inflammation per se to chronic pain conditions. Most previous microarray studies of DRG gene expression have investigated neuropathic pain models. To examine the role of inflammation, we used microarray methods to examine gene expression 3 days after local inflammation of the L5 DRG in rat. We observed significant regulation in a large number of genes (23% of observed transcripts), and examined 221 (3%) with a fold-change of 1.5-fold or more in more detail. Immune-related genes were the largest category in this group and included members of the complement system as well as several pro-inflammatory cytokines. However, these upregulated cytokines had no prior links to peripheral pain in the literature other than through microarray studies, though most had previously described roles in CNS (especially neuroinflammatory conditions) as well as in immune responses. To confirm an association to pain, qPCR studies examined these cytokines at a later time (day 14), as well as in two different versions of the spinal nerve ligation pain model including a version without any foreign immunogenic material (suture). Cxcl11, Cxcl13, and Cxcl14 were found to be significantly upregulated in all these conditions, while Cxcl9, Cxcl10, and Cxcl16 were upregulated in at least two of these conditions.