dizocilpine-maleate and Sciatica

We have previously demonstrated that parathyroid hormone 2 (PTH2) receptors are expressed in dorsal root ganglion (DRG) neurons and that its endogenous agonist tuberoinfundibular peptide of 39 residues (TIP39) causes nociceptive paw flexor responses after intraplantar administration. Here we found that the PTH2 receptor is selectively localized on myelinated A-, but not unmyelinated C-fibers using immunohistochemical labeling, based on PTH2 receptor expression on antibody N52-positive medium/large-sized DRG neurons, but not on TRPV1, substance P, P2X(3) receptor or isolectin B4-binding protein-positive small-sized DRG neurons. Pharmacological studies showed that TIP39-induced nociceptive responses were mediated by activation of G(s) and cAMP-dependent protein kinase. We also found that nociceptive responses induced by TIP39- or the cAMP analog 8-bromo-cAMP were significantly greater following partial sciatic nerve injury induced neuropathic pain, without changes in PTH2 receptor expression. Together these data suggest that activation of PTH2 receptors stimulates nociceptive A-fiber through G(s)-cAMP-dependent protein kinase signaling, and this pathway has elevated sensitization following nerve injury.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Behavior, Animal; Capsaicin; Disease Models, Animal; Dizocilpine Maleate; Dose-Response Relationship, Drug; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Ganglia, Spinal; Gene Expression Regulation; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Nerve Fibers, Myelinated; Neurons; Neuropeptides; Pain; Pain Measurement; Piperidines; Receptor, Parathyroid Hormone, Type 2; Reflex; Sciatica; Signal Transduction; Time Factors; TRPV Cation Channels

The effects of electrical stimulation of the sciatic nerve on background electromyographic and static stretch reflex activity of the trunk muscles were studied.. To verify the hypotheses that sciatic scoliosis is induced reflexively by radiculopathic pain, and that scoliosis might be maintained by prolonged asymmetric alteration of the trunk muscle tonus caused by central sensitization of the spinal neurons that constitute the postural reflex pathways.. Sciatic scoliosis usually occurs with convexity to the side of the herniated disc. The neuronal mechanism of sciatic scoliosis has not been well clarified. Recently, prolonged alteration of motor function in the hindlimbs of animals caused by central sensitization has been reported.. In spinalized rats (transection of the spinal cord), the sciatic nerve was stimulated electrically as a conditioning stimulus. Muscle stretch elicited by bending of the lumbar spine was applied as a test stimulus. Background and stretch reflex activities of the bilateral oblique abdominal, psoas, and quadratus lumborum muscles were recorded. Rats in which MK-801, an N-methyl-d-aspartate antagonist, was preadministered also were used.. The conditioning stimulus enhanced background electromyographic activity in bilateral oblique abdominal, contralateral psoas, and quadratus lumborum muscles. Furthermore, the conditioning stimulus induced prolonged facilitation and depression of stretch reflex activity of the contralateral psoas and quadratus lumborum, and ipsilateral psoas and quadratus lumborum muscles, respectively. Preadministration of MK-801 reduced these excitatory and inhibitory effects.. It was found that the pattern of electromyographic activity of the trunk muscles evoked by sciatic nerve stimulation coincided with the typical direction of sciatic scoliosis in patients with lumbar disc herniation. It was supposed that the prolonged asymmetric alteration of the trunk muscle tonus was caused by central sensitization, and that central sensitization of spinal neurons may underlie the neuronal mechanism of sciatic scoliosis.

Topics: Animals; Dizocilpine Maleate; Electric Stimulation; Electromyography; Excitatory Amino Acid Antagonists; Male; Muscle, Skeletal; Nerve Fibers; Nociceptors; Posterior Horn Cells; Radiculopathy; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Reflex, Stretch; Sciatic Nerve; Sciatica; Scoliosis