Peripheral formalin injury induces 2 stages of microglial activation in the spinal cord.
The formalin test produces 2 well-known acute phases of nociceptive behavior. Recently, we have shown that this same formalin test produces a third phase of nociceptive behavior consisting of prolonged thermal and mechanical hyperalgesia beginning days after formalin injection and lasting for at least 3 weeks. Here we investigated the activity of 3 MAPKs (p38, ERK and JNK) in the spinal dorsal horn following 5% formalin injection into rat hind paw. The p38 MAPK was rapidly activated in the spinal microglia minutes after injection and the activation persisted for 1 hour. In addition, this same injury induced a secondary increase of phospho-p38 expression in spinal microglia that was maximal 3 to 7 days postinjection. Intrathecal administration of p38 inhibitor SB203580 not only inhibited the early acute spontaneous nociceptive behaviors, but also inhibited the long-term formalin injury-induced mechanical hyperalgesia. Our results suggest that peripheral formalin injection induces 2 stages of microglial activation, and p38 activation in spinal microglia plays key roles in central pain modulation in formalin test respectively for the early acute phases and the late secondary long-term pain state as well.


CONCLUSIONS
This article presents unique properties of spinal microglial activation in a pain animal model. This finding could potentially help clinicians to further understand the contributions of spinal microglia to acute and chronic pain state.
Li
Kai
K
Center for TMD & Orofacial Pain, Peking University School & Hospital of Stomatology, Beijing 100081, P R China.
Lin
Ting
T
Cao
Ye
Y
Light
Alan R
AR
Fu
Kai-Yuan
KY
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D009619:Nociceptors / Q000187:drug effects / Q000201:enzymology; D010147:Pain Measurement / Q000379:methods; D010148:Intractable Pain / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*
D047428:Protein Kinase Inhibitors