RT Journal Article
SR Electronic
T1 TRPM2 Contributes to Inflammatory and Neuropathic Pain through the Aggravation of Pronociceptive Inflammatory Responses in Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3931
OP 3941
DO 10.1523/JNEUROSCI.4703-11.2012
VO 32
IS 11
A1 Kayo Haraguchi
A1 Ai Kawamoto
A1 Kouichi Isami
A1 Sanae Maeda
A1 Ayaka Kusano
A1 Kayoko Asakura
A1 Hisashi Shirakawa
A1 Yasuo Mori
A1 Takayuki Nakagawa
A1 Shuji Kaneko
YR 2012
UL http://www.jneurosci.org/content/32/11/3931.abstract
AB Accumulating evidence suggests that neuroimmune interactions contribute to pathological pain. Transient receptor potential melastatin 2 (TRPM2) is a nonselective Ca2+-permeable cation channel that acts as a sensor for reactive oxygen species. TRPM2 is expressed abundantly in immune cells and is important in inflammatory processes. The results of the present study show that TRPM2 plays a crucial role in inflammatory and neuropathic pain. While wild-type and TRPM2 knock-out mice showed no difference in their basal sensitivity to mechanical and thermal stimulation, nocifensive behaviors in the formalin test were reduced in TRPM2 knock-out mice. In carrageenan-induced inflammatory pain and sciatic nerve injury-induced neuropathic pain models, mechanical allodynia and thermal hyperalgesia were attenuated in TRPM2 knock-out mice. Carrageenan-induced inflammation and sciatic nerve injury increased the expression of TRPM2 mRNA in the inflamed paw and around the injured sciatic nerve, respectively. TRPM2 deficiency diminished the infiltration of neutrophils and the production of chemokine (C-X-C motif) ligand-2 (CXCL2), a major chemokine that recruits neutrophils, but did not alter the recruitment of F4/80-positive macrophages in the inflamed paw or around the injured sciatic nerve. Microglial activation after nerve injury was suppressed in the spinal cord of TRPM2 knock-out mice. Furthermore, CXCL2 production and inducible nitric oxide synthase induction were diminished in cultured macrophages and microglia derived from TRPM2 knock-out mice. Together, these results suggest that TRPM2 expressed in macrophages and microglia aggravates peripheral and spinal pronociceptive inflammatory responses and contributes to the pathogenesis of inflammatory and neuropathic pain.