Abstract
Pain perception is altered during senescence and it is thought that this could in part be due to changes in peripheral pain sensing processes. The present study examined the effect of substance P (SP) (10−10−10−8 mol; 0.1 mL bolus close intraarterial) on knee joint afferent mechanosensitivity in young (2- to 5-mo-old) and aged (17- to 36-mo-old) Dunkin-Hartley guinea pigs. Single unit electrophysiological recordings were made from knee joint primary afferent nerves in response to normal (nonnoxious) and painful (noxious) rotation of the joint. In young and old animals, local application of SP had a sensitizing effect on joint afferents in response to movements made in the normal working range of the knee. With noxious hyper-rotation of the joint, SP was able to increase afferent firing rate in young but not in old animals. These data demonstrate a lack of SP-mediated sensitization of joint nociceptors during senescence and suggest a peripheral deficiency in joint nociception with respect to age.
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Bendele A. M. and Hulman J. F. (1988) Spontaneous cartilage degeneration in guinea pigs. Arthritis Rheum. 31, 561–565.
Berg B. N., Wolf A., and Simmshs (1962) Degenerative lesions of spinal roots and peripheral nerves in aging rats. Gerontologia 6, 72–80.
Bergman E., Johnson H., Zhang X., Hokfelt T., and Ulfhake B. (1996) Neuropeptides and neurotrophin receptor mRNAs in primary sensory neurons of aged rats. J. Comp. Neurol. 375, 303–319.
Carlton S. M., Zhou S., and Coggeshall R. E. (1996) Localization and activation of substance P receptors in unmyelinated axons of rat glabrous skin. Brain Res. 734, 103–108.
Cruce W. L., Lovell J. A., Crisp T., and Stuesse S. L. (2001) Effect of aging on the substance P receptor, NK-1, in the spinal cord of rats with peripheral nerve injury. Somatosens. Mot. Res. 18, 66–75.
de Paulis A., Marino I., Ciccarelli A., et al. (1996) Human synovial mast cells. I. Ultrastructural in situ and in vitro immunologic characterization. Arthritis Rheum. 39, 1222–1233.
Dhall U., Cowen T., Haven A. J., and Burnstock G. (1986) Perivascular noradrenergic and peptide-containing nerves show different patterns of changes during development and ageing in the guinea-pig. J. Auton. Nerv. Sys. 16, 109–126.
Felson D. T. (1995) The epidemiology of osteoarthritis: prevalence and risk factors, in Osteoarthritic Disorders (Kuettner K. E. and Goldberg C. H., eds). American Academy of Orthopaedic Surgeons, Rosemont, IL: pp 13–24.
Gibson S. J. and Farrell M. (2004) A review of age differences in the neurophysiology of nociception and the perceptual experience of pain. Clin. J. Pain 20, 227–239.
Grigg P., Schaible H. G., and Schmidt R. F. (1986) Mechanical sensitivity of group III and IV afferents from posterior articular nerve in normal and inflamed cat knee. J. Neurophysiol. 55, 635–643.
Guilbaud G., Iggo A., and Tegner R. (1985) Sensory receptors in ankle joint capsules of normal and arthritic rats. Exp. Brain Res. 58, 29–40.
Hanesch U., Pawlak M., and McDougall J. J. (2003) Gabapentin reduces the mechanosensitivity of fine afferent nerve fibres in normal and inflamed rat knee joints. Pain 104, 363–366.
Hannan M. T., Felson D. T., and Pincus T. (2000) Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J. Rheumatol. 27, 1513–1517.
Harkins S. W. and Chapman C. R. (1976) Detection and decision factors in pain perception in young and elderly men. Pain 2, 253–264.
Harkins S. W. and Chapman C. R. (1977) The perception of induced dental pain in young and elderly women. J. Gerontol. 32, 428–435.
Heppelmann B. and Pawlak M. (1997) Sensitisation of articular afferents in normal and inflamed knee joints by substance P in the rat. Neurosci. Lett. 223, 97–100.
Heppelmann B. and McDougall J. J. (2005) Inhibitory effect of amiloride and gadolinium on fine afferent nerves in the rat knee. Evidence of mechanogated ion channels in joints. Exp. Brain Res. 167, 114–118.
Heppelmann B., Messlinger K., Neiss W. F., and Schmidt R. F. (1995) Fine sensory innervation of the knee joint capsule by group III and group IV nerve fibers in the cat. J. Comp. Neurol. 351, 415–428.
Huebner J. L., Hanes M. A., Beekman B., TeKoppele J. M., and Kraus V. B. (2002) A comparative analysis of bone and cartilage metabolism in two strains of guinea-pig with varying degrees of naturally occurring osteoarthritis. Osteoarthritis Cart. 10, 758–767.
Hukkanen M., Grönblad M., Rees R., et al. (1991) Regional distribution of mast cells and peptide containing nerves in normal and adjuvant arthritic rat synovium. J. Rheumatol. 18, 177–183.
Jinks C., Jordan K., and Croft P. (2002) Measuring the population impact of knee pain and disability with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain 100, 55–64.
Kitagawa J., Kanda K., Sugiura M., et al. (2005) Effect of chronic inflammation on dorsal horn nociceptive neurons in aged rats. J. Neurophysiol. 93, 3594–3604.
Lawrence R. C., Helmick C. G., Arnett F. C., et al. (1998) Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 41, 778–799.
McDougall J. J., Pawlak M., Hanesch U., and Schmidt R. F. (2000) Peripheral modulation of rat knee joint afferent mechanosensitivity by nociceptin/orphanin FQ. Neurosci. Lett. 288, 123–126.
McDougall J. J., Hanesch U., Pawlak M., and Schmidt R. F. (2001) Participation of NK1 receptors in nociceptin-induced modulation of rat knee joint mechanosensitivity. Exp. Brain Res. 137, 249–253.
Pawlak M., Schmidt R. F., Heppelmann B., and Hanesch U. (2001) The neurokinin-1 receptor antagonist RP 67580 reduces the sensitization of primary afferents by substance P in the rat. Eur. J. Pain 5, 69–79.
Piotrowski W. and Foreman J. C. (1985) On the actions of substance P, somatostatin, and vasoactive intestinal polypeptide on rat peritoneal mast cells and in human skin. Naunyn-Schmiedeberg’s Arch. Pharmacol. 331, 364–368.
Sakai K., Matsuno H., Tsuji H., and Tohyama M. (1998) Substance P receptor (NK1) gene expression in synovial tissue in rheumatoid arthritis and osteoarthritis. Scand. J. Rheumatol. 27, 135–141.
Samorajski T. (1974) Age differences in the morphology of posterior tibial nerves of mice. J. Comp. Neurol. 157, 439–445.
Schaible H. G. and Schmidt R. F. (1983a) Responses of fine medial articular nerve afferents to passive movements of knee joints. J. Neurophysiol. 49, 1118–1126.
Schaible H. G. and Schmidt R. F. (1983b) Activation of groups III and IV sensory units in medial articular nerve by local mechanical stimulation of knee joint. J. Neurophysiol. 49, 35–44.
Schaible H. G. and Schmidt R. F. (1985) Effects of an experimental arthritis on the sensory properties of fine articular afferent units. J. Neurophysiol. 54, 1109–1122.
Schepelmann K., Messlinger K., Schaible H. G., and Schmidt R. F. (1992) Inflammatory mediators and nociception in the joint: excitation and sensitization of slowly conducting afferent fibers of cat’s knee by prostaglandin 12. Neurosci. 50, 237–247.
Schuelert N. and McDougall J. J. (2006) Electrophysiological evidence that the vasoactive intestinal peptide receptor antagonist VIP(6–28) reduces nociception in an animal model of osteoarthritis. Osteoarthritis Cart. 14, 1155–1162.
Sharma A. K., Bajada S., and Thomas P. K. (1980) Age changes in the tibial and plantar nerves of the rat. J. Anat. 130, 417–428.
Skofitsch G., Donnerer J., Petronijevic S., Saria A., and Lembeck F. (1983) Release of histamine by neuropeptides from the perfused rat hindquarter. Naunyn-Schmiedeberg’s Arch. Pharmacol. 322, 153–157.
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McDougall, J.J., Schuelert, N. Age alters the ability of substance P to sensitize joint nociceptors in Guinea pigs. J Mol Neurosci 31, 289–296 (2007). https://doi.org/10.1385/JMN:31:03:289
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DOI: https://doi.org/10.1385/JMN:31:03:289