Increase in hemokinin-1 mRNA in the spinal cord during the early phase of a neuropathic pain state.
OBJECTIVE
Substance P (SP), a representative member of the tachykinin family, is involved in nociception under physiological and pathological conditions. Recently, hemokinin-1 (HK-1) was identified as a new member of this family. Although HK-1 acts on NK(1) tachykinin receptors that are thought to be innate for SP, the roles of HK-1 in neuropathic pain are still unknown.


METHODS
Using rats that had been subjected to chronic constrictive injury (CCI) of the sciatic nerve as a neuropathic pain model, we examined the changes in expression of SP- and HK-1-encoding genes (TAC1 and TAC4, respectively) in the L4/L5 spinal cord and L4/L5 dorsal root ganglia (DRGs) in association with changes in pain-related behaviours in this neuropathic pain state.


RESULTS
The TAC4 mRNA level was increased on the ipsilateral side of the dorsal spinal cord, but not in DRGs, at day 3 after CCI. In contrast, the TAC1 mRNA level was significantly increased in the DRGs at day 3 after CCI without any changes in the dorsal spinal cord. Analysis of a cultured microglial cell line revealed the presence of TAC4 mRNA in microglial cells. Minocycline, an inhibitor of microglial activation, blocked the increased expression of TAC4 mRNA after CCI and inhibited the associated pain-related behaviours and microglial activation in the spinal cord.


CONCLUSIONS
The present results suggest that HK-1 expression is increased at least partly in activated microglial cells after nerve injury and is clearly involved in the early phase of neuropathic pain.
Matsumura
T
T
Anesthesiology and Clinical Physiology, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Sakai
A
A
Nagano
M
M
Sawada
M
M
Suzuki
H
H
Umino
M
M
Suzuki
H
H
D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012585:Sciatica / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015320:Tachykinins / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D015320:Tachykinins; C507968:hemokinin-1; D008911:Minocycline