Spinal distribution of c-Fos activated neurons expressing enkephalin in acute and chronic pain models.
The endogenous opioid enkephalin is known to inhibit spinal nociceptive transmission. Here we investigated activation of spinal enkephalinergic neurons by determining the proportions of c-Fos expressing (activated) spinal neurons that were enkephalinergic after different acute and chronic peripheral nociceptive stimuli. The number of c-Fos-activated neurons in the dorsal horn was increased after hind paw injection of capsaicin, formalin or complete Freund's adjuvant (CFA, 1.5 hrs - 4 days). The numbers of these neurons that were enkephalinergic increased after paraformaldehyde, and at 20 hrs, but not 1.5 hrs or 4 days post-CFA as compared to saline. In the spared nerve injury (SNI) model of neuropathic pain, c-Fos expression was increased acutely (2 hrs) and chronically (2 weeks), and a greater number of these were enkephalinergic in the nerve-injured animals acutely compared to controls (sham-SNI). Combining all acute (=2 hrs) versus chronic (≥20 hrs) treatment groups, there was a significant decrease in the percentage of activated neurons that were enkephalinergic in superficial layers, but a significant increase in the deeper layers of the dorsal horn in the chronic treatment group. It is concluded that the overall percentage of c-Fos activated neurons that contained enkephalin was not significantly different between acute and chronic pain phases. However, the shift in localization of these neurons within the spinal dorsal horn indicates a noxious stimulus directed activation pattern.
Department of Neuroscience, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Mehdi
M
Hossaini
Department of Plastic Reconstructive and Hand Surgery, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Liron S
LS
Duraku
Department of Neuroscience, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Somesh K
SK
Kohli
Department of Neurology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Joost L M
JL
Jongen
Department of Neuroscience, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: j.holstege@erasmusmc.nl.
Jan C
JC
Holstege
D000704:Analysis of Variance; D000818:Animals; D002211:Capsaicin / Q000633:toxicity; D004195:Disease Models, Animal; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005557:Formaldehyde / Q000633:toxicity; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000473:pathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011108:Polymers / Q000633:toxicity; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000473:pathology*; D013997:Time Factors
D004745:Enkephalins; D011108:Polymers; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D005557:Formaldehyde; D005620:Freund's Adjuvant; C033660:preproenkephalin; D002211:Capsaicin; C003043:paraform
Enkephalin; Fos; Inflammation; Neuropathic; Pain; Spinal