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The Journal of Neuroscience, August 15, 2000, 20(16):6302-6308

Mechanisms for Ovariectomy-Induced Hyperalgesia and Its Relief by Calcitonin: Participation of 5-HT_1A-Like Receptor on C-Afferent Terminals in Substantia Gelatinosa of the Rat Spinal Cord

Akitoshi Ito^{1, 2}, Eiichi Kumamoto¹, Mitsuhiro Takeda², Mineko Takeda², Kensuke Shibata², Hitoshi Sagai², and Megumu Yoshimura¹

¹ Department of Physiology, Saga Medical School, Saga 849-8501, Japan, and ² Laboratory for Pharmacology, Institute for Life Science Research, Asahi Chemical Industry Co. Ltd., Ohito, Shizuoka 410-2321, Japan

Chronic treatment with calcitonin in osteoporotic patients alleviates the pain associated with this condition by an unknown mechanism. In ovariectomized rats that develop osteoporosis and hyperalgesia, we examined whether a functional change in serotonergic systems in the spinal dorsal horn was involved, using whole-cell recordings from substantia gelatinosa neurons in spinal cord slices and [³H]8-hydroxy-2(di-n-propylamino)tetralin ([³H]8-OH-DPAT) binding. Hyperalgesia could be attributed to the elimination of presynaptic inhibition by 5-HT of glutamatergic primary C-afferent terminals and an associated decrease in the density of [³H]8-OH-DPAT binding sites whose receptors are neither 5-HT_1A- nor 5-HT₇-subtype. These changes in serotonergic systems were restored after chronic treatment with calcitonin. Reversal of 5-HT receptor changes by calcitonin treatment may provide an explanation for its analgesic actions in patients.

Key words: serotonin; substantia gelatinosa; EPSC; spinal cord slice; patch-clamp; ovariectomy; hyperalgesia; calcitonin; plasticity

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20166302-07$05.00/0

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