Post-inflammatory
pain is a poorly understood phenomenon.
G protein-coupled receptors are involved in regulating
pain signaling in the context of
inflammation.
G protein-coupled receptor kinases (GRK) modulate signaling through these receptors. We investigated whether GRK6 contributes to post-inflammatory visceral
hyperalgesia.
Colitis was induced in female mice by 1%
dextran sodium sulphate in
drinking water for 7 days. Disease score, colon length, and colonic
cytokines were determined. On day 49, when animals had recovered from
colitis, we induced
visceral pain by intracolonic
capsaicin instillation. Behavioral responses to
capsaicin were monitored for 20 min. Referred
hyperalgesia was measured using von Frey hairs. Spinal cord c-Fos was visualized by immunohistochemistry. In contrast to our earlier observations in male GRK6-/- and wild type (WT) mice, we did not detect differences in the course of
colitis or in expression of colonic
cytokines between female GRK6-/- and WT mice. After recovery from
colitis,
capsaicin-induced behavioral
pain responses and spinal cord c-Fos expression were more pronounced in female GRK6-/- than WT mice. Naive GRK6-/- and WT animals did not differ in
pain and c-Fos responses to
capsaicin.
Capsaicin-induced referred
hyperalgesia post-
colitis was increased in GRK6-/- compared to WT mice. However, referred
hyperalgesia post-
colitis was not affected by ablation of GRK6. Furthermore, in vitro IL-1beta sensitized the
capsaicin receptor TRPV1 and this process was inhibited by over-expression of GRK6. We describe the novel concept that GRK6 inhibits post-inflammatory visceral
hyperalgesia but does not contribute to
visceral pain in naive animals. We propose that GRK6 regulates
inflammation-induced sensitization of TRPV1.