title: Differential distribution of activated spinal neurons containing glycine and/or GABA and expressing c-fos in acute and chronic pain models.
abstract: The inhibitory transmitters GABA and glycine play an important role in modulating pain transmission, both in normal and in pathological situations. In the present study we have combined in situ hybridization for identifying spinal neurons that use the transmitter(s) glycine and/or GABA (Gly/GABA neurons) with immunohistochemistry for c-fos, a marker for neuronal activation. This procedure was used with acute pain models induced by the injection of capsaicin or formalin; and chronic pain models using Complete Freund's Adjuvant (CFA, chronic inflammation), and the spared nerve injury (SNI) model (neuropathic pain). In all models Gly/GABA neurons were activated as indicated by their expression of c-fos. The pattern of Gly/GABA neuronal activation was different for every model, both anatomically and quantitatively. However, the averaged percentage of activated neurons that were Gly/GABA in the chronic phase (≥20h survival, 46%) was significantly higher than in the acute phase (≤2h survival, 34%). In addition, the total numbers of activated Gly/GABA neurons were similar in both phases, showing that the activation of non-Gly/GABA (presumed excitatory) neurons in the chronic phase decreased. Finally, morphine application equally decreased the total number of activated neurons and activated Gly/GABA neurons. This showed that morphine did not specifically activate Gly/GABA neurons to achieve nociceptive inhibition. The present study shows an increased activity of Gly/GABA neurons in acute and chronic models. This mechanism, together with mechanisms that antagonize the effects of GABA and glycine at the receptor level, may determine the sensitivity of our pain system during health and disease.
authors: Department of Neuroscience, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands Department of Plastic Reconstructive and Hand Surgery, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands Department of Neurology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors: Mehdi
authors: M
authors: Hossaini
authors: Liron S
authors: LS
authors: Duraku
authors: Çiğdem
authors: Ç
authors: Saraç
authors: Joost L M
authors: JLM
authors: Jongen
authors: Jan C
authors: JC
authors: Holstege
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000009:adverse effects; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000145:classification / Q000473:pathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013116:Spinal Cord / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D005557:Formaldehyde; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D002211:Capsaicin; D005998:Glycine