Mechanisms for Ovariectomy-Induced Hyperalgesia and Its Relief by Calcitonin: Participation of 5-HT1A-Like Receptor on C-Afferent Terminals in Substantia Gelatinosa of the Rat Spinal Cord

• DOI: 10.1523/jneurosci.20-16-06302.2000
• Publication Date: 2018-04-03T22:05:13Z
• Authors: Akitoshi Ito; Eiichi Kumamoto; Mitsuhiro Takeda; Mineko Takeda; Kensuke Shibata; Hitoshi Sagai; Megumu Yoshimura
• Keywords: Calcitonin; 8-Hydroxy-2-(di-n-propylamino)tetralin; Serotonin; Binding Sites; Ovariectomy; Presynaptic Terminals; Synaptic Membranes; Excitatory Postsynaptic Potentials; Nociceptors; Tritium; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Nerve Fibers; 0302 clinical medicine; Hyperalgesia; Receptors, Serotonin; Animals; Osteoporosis; Female; Receptors, Serotonin, 5-HT1

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 [(3)H]8-hydroxy-2(di-n-propylamino)tetralin ([(3)H]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 [(3)H]8-OH-DPAT binding sites whose receptors are neither 5-HT(1A)- nor 5-HT(7)-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.