Neuromedin U receptor 2 does not play a role in the development of neuropathic pain following nerve injury in mice.
BACKGROUND
Previous studies have identified neuromedin U receptor 2 (NMUR2) as the subtype mediating the effects of neuromedin U on acute chemo-nociception induced by capsaicin or formalin injection. The aims of this study were to determine whether NMUR2 is required for the development of mechanical hypersensitivity after nerve injury or heat hypersensitivity after inflammation and whether there is a gender difference in the contribution of NMUR2 to nociception.


METHODS
Mechanical sensitivity was assessed with von Frey filaments in wild type (WT) and NMUR2-null mice at baseline and following spared tibial nerve (STN) injury. Heat sensitivity was also assessed at baseline and after induction of inflammation with Freund's complete adjuvant (FCA).


RESULTS
The response to von Frey filaments at baseline was similar for WT and NMUR2-null mice and for males and females. The response of male NMUR2-null mice was slightly but significantly decreased when exposed to 52 °C but not 58 °C heat stimuli. There was no difference between the stimulus-response curve for WT and NMUR2-null mice 7, 13 and 16 days after nerve injury. Similarly, after FCA-induced inflammation, there was no significant difference in heat hyperalgesia between WT and NMUR2-null mice or male or female mice in responses to temperatures ranging from 44 to 48 °C.


CONCLUSIONS
The present data do not support a significant contribution of NMUR2 to the development of hypersensitivity after nerve injury or tissue inflammation, suggesting that pharmacological intervention aimed at the NMUR2 receptor might not be a valuable approach for the treatment of chronic pain.
AstraZeneca R&D Montreal, CNS&Pain Innovative Medicines Unit, Montreal, Canada.
A K
AK
Gilbert
C
C
Puma
X
X
Xu
J M A
JM
Laird
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009437:Neuralgia / Q000235:genetics*; D009479:Neuropeptides / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000139:chemically induced / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000235:genetics*
D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U