GlyR alpha3 has previously been found to play a critical role in
pain hypersensitivity following spinal
PGE(2) injection, complete
Freund's adjuvant (CFA) and
zymosan induced peripheral
inflammation. In this study, although all models displayed typical phenotypic behaviours, no significant differences were observed when comparing the
pain behaviours of Glra3(-/-) and wild-type littermates following the injection of
capsaicin,
carrageenan,
kaolin/
carrageenan or
monosodium iodoacetate, models of rheumatoid and
osteoarthritis, respectively. However, clear differences were observed following CFA injection (p < 0.01). No significant differences were observed in the
pain behaviours of Glra3(-/-) and wild-type littermates following experimentally induced
neuropathic pain (partial sciatic nerve
ligation). Similarly, Glra3(-/-) and wild-type littermates displayed indistinguishable visceromotor responses to colorectal distension (a model of
visceral pain) and in vivo spinal cord dorsal horn electrophysiology revealed no differences in responses to multimodal suprathreshold stimuli, intensities which equate to higher
pain scores such as those reported in the clinic. These data suggest that apart from its clear role in CFA- and
zymosan-induced
pain sensitisation,
hypersensitivity associated with other models of
inflammation, neuropathy and visceral disturbances involves mechanisms other than the EP2 receptor -
GlyR alpha3 pathway.