Khasabov SG, Ghilardi JR, Mantyh PW, Simone DA (2003) Spinal neurons that possess the substance P receptor (SPR) modulate descending systems that control excitability of spinal nociceptive neurons. Neuroscience 2003 Abstracts 13.3. Society for Neuroscience, New Orleans, LA.
Summary: We have recently shown that ablation of spinal SPR-expressing spinal neurons by intrathecal application of the cytotoxin conjugate substance P-saporin (SP-SAP) prevents the development of sensitization produced by intraplantar injection of capsaicin (Khasabov et al., 2002) and reduced hyperalgesia produced by inflammation and nerve injury (Mantyh et al., 1997; Nichols et al., 1999). Since the majority of spinal SPR-expressing neurons project to the brain, it is possible that these neurons are an integral part of ascendingdescending circuitry that modulates excitability of spinal nociceptive neurons. Here we studied the contribution of ascending SPR positive neurons in the regulation of brain stem descending pathways that pass through the dorsolateral funiculus (DLF) and modulate spinal cord excitability and sensitization. Rats were given an intrathecal injection of vehicle (0.9% NaCl, 10μl) or SP-SAP (5·10-6M, 10μl) at the lumbar enlargement 30 days prior to electrophysiological recording from lumbar spinal neurons. Spontaneous activity and evoked responses of nociceptive neurons to heat (35-51.°C) and mechanical stimuli (von Frey monofilaments) were obtained before and 1 hour after ipsilateral DLF transection. In vehicle-treated animals, DLF transection produced a 183% increase spontaneous activity, a leftward shift in the temperature-response curve, and a 60% increase in the number of impulses evoked by mechanical stimuli (n=25). In contrast, neurons in the SP-SAP group did not show any changes in spontaneous or evoked activity after DLF transaction (n=29). We conclude that ascending spinal SPR-possessing neurons modulate activity of descending inhibitory systems that pass through the DLF.
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