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Possible mechanism of c-fos expression in trigeminal nucleus caudalis following cortical spreading depression.
Pain 1997; 72(3):407-15PAIN

Abstract

Cortical spreading depression (CSD) is characterized by a transient, reversible depression of EEG activity which advances across the cortical surface at a velocity of 2-5 mm/min. CSD was originally linked to the aura phase of migraine, but recently also to migraine headache. The theory is that CSD activates meningeal trigeminal C-fibers causing neurogenic inflammation and pain (Moskowitz, M.A., Nozaki, K. and Kraig, R.P., Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms, J. Neurosci., 13 (1993) 1167-1177). The present study is an examination of the proposed link between CSD elicited in rats and activation of trigeminal nerve fibers. Multiple CSDs were elicited unilaterally for 1 h by KCl injections (1 M, 5 microliters) into the right hemisphere, while NaCl (1 M, 5 microliters) was injected into the left as control. After an additional 1 h the animals were sacrificed and trigeminal activation assessed by the expression of c-fos in trigeminal nucleus caudalis (TNC) using immunohistochemistry. The correlation between the number of CSDs and the extent of c-fos expression was determined. In addition the effect of sumatriptan (0.3 mg/kg) and morphine (3 mg/kg) given i.v. 30 min before elicitation of CSD was evaluated. CSD caused increased c-fos expression in lamina I and II of TNC where C-fibers, end, the response being greater ipsilaterally. Morphine, but not sumatriptan, reduced c-fos expression in both the ipsilateral and contralateral TNC by 71% (P < 0.05 and P = 0.19, respectively), confirming that nociceptors have been activated. No positive correlation was seen between the number of CSDs and the extent of c-fos expression in TNC. Instead we observed a positive, linear correlation between the number of KCl injections and the extent of c-fos expression in TNC (correlation coefficient r = 0.709, P < 0.05). We suggest that the C-fiber activation observed is caused by hyperosmolar KCl/NaCl and not CSD. Hence, our results do not support the hypothesis of Moskowitz et al. (Moskowitz, M.A., Nozaki, K. and Kraig, R.P., Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms, J. Neurosci., 13 (1993) 1167-1177) which links CSD with migraine headache.

Authors+Show Affiliations

Department of General Pharmacology, Novo Nordisk A/S, Maaloev, Denmark. bkin@novo.dkNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9313281

Citation

Ingvardsen, B K., et al. "Possible Mechanism of C-fos Expression in Trigeminal Nucleus Caudalis Following Cortical Spreading Depression." Pain, vol. 72, no. 3, 1997, pp. 407-15.
Ingvardsen BK, Laursen H, Olsen UB, et al. Possible mechanism of c-fos expression in trigeminal nucleus caudalis following cortical spreading depression. Pain. 1997;72(3):407-15.
Ingvardsen, B. K., Laursen, H., Olsen, U. B., & Hansen, A. J. (1997). Possible mechanism of c-fos expression in trigeminal nucleus caudalis following cortical spreading depression. Pain, 72(3), pp. 407-15.
Ingvardsen BK, et al. Possible Mechanism of C-fos Expression in Trigeminal Nucleus Caudalis Following Cortical Spreading Depression. Pain. 1997;72(3):407-15. PubMed PMID: 9313281.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Possible mechanism of c-fos expression in trigeminal nucleus caudalis following cortical spreading depression. AU - Ingvardsen,B K, AU - Laursen,H, AU - Olsen,U B, AU - Hansen,A J, PY - 1997/10/6/pubmed PY - 1997/10/6/medline PY - 1997/10/6/entrez SP - 407 EP - 15 JF - Pain JO - Pain VL - 72 IS - 3 N2 - Cortical spreading depression (CSD) is characterized by a transient, reversible depression of EEG activity which advances across the cortical surface at a velocity of 2-5 mm/min. CSD was originally linked to the aura phase of migraine, but recently also to migraine headache. The theory is that CSD activates meningeal trigeminal C-fibers causing neurogenic inflammation and pain (Moskowitz, M.A., Nozaki, K. and Kraig, R.P., Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms, J. Neurosci., 13 (1993) 1167-1177). The present study is an examination of the proposed link between CSD elicited in rats and activation of trigeminal nerve fibers. Multiple CSDs were elicited unilaterally for 1 h by KCl injections (1 M, 5 microliters) into the right hemisphere, while NaCl (1 M, 5 microliters) was injected into the left as control. After an additional 1 h the animals were sacrificed and trigeminal activation assessed by the expression of c-fos in trigeminal nucleus caudalis (TNC) using immunohistochemistry. The correlation between the number of CSDs and the extent of c-fos expression was determined. In addition the effect of sumatriptan (0.3 mg/kg) and morphine (3 mg/kg) given i.v. 30 min before elicitation of CSD was evaluated. CSD caused increased c-fos expression in lamina I and II of TNC where C-fibers, end, the response being greater ipsilaterally. Morphine, but not sumatriptan, reduced c-fos expression in both the ipsilateral and contralateral TNC by 71% (P < 0.05 and P = 0.19, respectively), confirming that nociceptors have been activated. No positive correlation was seen between the number of CSDs and the extent of c-fos expression in TNC. Instead we observed a positive, linear correlation between the number of KCl injections and the extent of c-fos expression in TNC (correlation coefficient r = 0.709, P < 0.05). We suggest that the C-fiber activation observed is caused by hyperosmolar KCl/NaCl and not CSD. Hence, our results do not support the hypothesis of Moskowitz et al. (Moskowitz, M.A., Nozaki, K. and Kraig, R.P., Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms, J. Neurosci., 13 (1993) 1167-1177) which links CSD with migraine headache. SN - 0304-3959 UR - https://www.unboundmedicine.com/medline/citation/9313281/Possible_mechanism_of_c_fos_expression_in_trigeminal_nucleus_caudalis_following_cortical_spreading_depression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304395997000699 DB - PRIME DP - Unbound Medicine ER -