Our long-term objectives is to elucidate the central mechanisms and neuroblastic underlying acute and chronic pain. While alterations in C- fiber function have been implicated in several chronic pain conditions, the role of C-fiber afferent in the normal development of neuronal properties in central somatosensory pathways, let alone in the development of disordered pain behavior, is still unclear. C-fibers do provide nociceptive afferent excitatory inputs to V brainstem and spinal and spinal neurons, but recent studies have drawn attention to the possible neuroeffector and neurotrophic influences that C fibers may also exert; these neuroblastic influence including shaping neuronal receptive field and response properties in both nociceptive and non-nociceptive pathways. Do C-fibers have a similar role in the normal development of these properties i the V somatosensory system? We will address this question, by testing: Hypothesis I, that the neonatal depletion of C- fiber afferent produces alterations in the receptive field and response properties of nociceptive neurons in subnucleus caudalis of the adult V brainstem complex; Hypothesis II, that the neonatal depletion of C-fiber afferent produces alterations in the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the subnucleus caudalis of the adult V brainstem complex; and Hypothesis III, that the neonatal depletion of C-fiber afferent produces alterations in the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the main sensory nucleus of the adult V brainstem complex. Since C-fiber primary afferent do not project to the V main sensory nucleus changes associated with neonatal capsaicin administration is an alteration to the modulatory influence that caudalis exerts on main sensory neurons; we will therefore also test: Hypothesis IV, that the neonatal depletion of C-fiber afferent produces alteration in the modulatory influences of subnucleus caudalis on the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the main sensory nucleus of the adult V brainstem complex. For each series of experiments, neonatal rats will be injected with capsaicin to deplete their C-fiber afferent and then at 2-3 months of age we will characterize, and compare with control animals, the properties of neurons in V subnucleus caudalis, which acts as the as the primary brainstem relay of nociceptive information, or in the main sensory nucleus which acts as the principal LTM brainstem relay in the vibrissa pathway to cortex. In both groups of animals, main sensory neuronal properties will also be tested during manipulation of the ascending caudalis modulatory influences by local anesthetic or glutamate injections of caudalis. The significance of these studies lies in their integral link to neuroblastic processes operating in the V brainstem complex and the determinants of receptive field and response properties of V somatosensory neurons, and to the view that altered C-fiber function may be involved in the development of several chronic pain conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE004786-17
Application #
2129002
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
1978-01-01
Project End
1996-05-31
Budget Start
1995-06-10
Budget End
1996-05-31
Support Year
17
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Toronto
Department
Type
DUNS #
259999779
City
Toronto
State
ON
Country
Canada
Zip Code
M5 1-S8
Yao, Dongyuan; Yoshida, Mitsuhiro; Sessle, Barry J (2015) Dura-evoked neck muscle activity involves purinergic and N-methyl-D-aspartate receptor mechanisms. Neuroreport 26:1155-60
Wang, Hua; Cao, Ye; Chiang, Chen-Yu et al. (2014) The gap junction blocker carbenoxolone attenuates nociceptive behavior and medullary dorsal horn central sensitization induced by partial infraorbital nerve transection in rats. Pain 155:429-35
Cao, Ye; Wang, Hua; Chiang, Chen-Yu et al. (2013) Pregabalin suppresses nociceptive behavior and central sensitization in a rat trigeminal neuropathic pain model. J Pain 14:193-204
Matsuura, Shingo; Shimizu, Kohei; Shinoda, Masamichi et al. (2013) Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation. PLoS One 8:e52840
Wang, H; Xie, Y F; Chiang, C Y et al. (2013) Central ?-adrenoceptors contribute to mustard oil-induced central sensitization in the rat medullary dorsal horn. Neuroscience 236:244-52
Cao, Ye; Li, Kai; Fu, Kai-Yuan et al. (2013) Central sensitization and MAPKs are involved in occlusal interference-induced facial pain in rats. J Pain 14:793-807
Kumar, Naresh; Cherkas, Pavel S; Varathan, Vidya et al. (2013) Systemic pregabalin attenuates facial hypersensitivity and noxious stimulus-evoked release of glutamate in medullary dorsal horn in a rodent model of trigeminal neuropathic pain. Neurochem Int 62:831-5
Kiyomoto, Masaaki; Shinoda, Masamichi; Okada-Ogawa, Akiko et al. (2013) Fractalkine signaling in microglia contributes to ectopic orofacial pain following trapezius muscle inflammation. J Neurosci 33:7667-80
Narita, N; Kumar, N; Cherkas, P S et al. (2012) Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model. Neuroscience 218:359-66
Kumar, Naresh; Cherkas, Pavel S; Chiang, C Y et al. (2012) Involvement of ATP in noxious stimulus-evoked release of glutamate in rat medullary dorsal horn: a microdialysis study. Neurochem Int 61:1276-9

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