Abstract
In 18 cats anaesthetized with alpha-chloralose, we recorded from thin myelinated and unmyelinated articular afferents of the medial articular nerve of the knee joint. Bradykinin was injected intra-arterially close to the knee, alone and in combination with prostaglandin E2 (PGE2), and changes of the responses of single afferents to movements of the knee were monitored. Bradykinin changed the mechanosensitivity in 20 of 28 afferents inducing movement sensitivity in initially unresponsive units, lowering the threshold for movements in high-threshold afferents and/ or enhancing pre-existing responses to innocuous and/or noxious joint movements in low and high threshold units. Also the application of PGE2 and bradykinin within a short interval sensitized the majority of these afferents, and in about 50% of the afferents the effect of the combination was superior to those induced by the single substances. We conclude that the inflammatory mediator bradykinin is able to sensitize articular afferents for movement stimuli and that PGE2 may enhance this effect. It is suggested that in arthritis inflammatory mediators act synergistically in the initiation and stabilization of the increased mechanosensitivity of slowly conducting articular afferents.
Similar content being viewed by others
References
Berberich P, Hoheisel U, Mense S (1988) Effects of a carrageenan-induced myositis on the discharge properties of group III and IV muscle receptors in the cat. J Neurophysiol 59:1395–1409
Brown DA, Higashida H (1988) Membrane current responses of NG108-15 mouse neuroblastoma x rat glioma hybrid cells to bradykinin. J Physiol (Lond) 397:167–184
Chahl LA (1979) Pain induced by inflammatory mediators. In: Beers RF, Bassett EG (eds) Mechanisms of pain and analgesic compounds. Raven, New York, pp 273–284
DiRosa M, Giroud JP, Willoughby DA (1971) Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol 104:15–29
Garcia Leme J (1978) Bradykininsystem. In: Vane JR, Ferreira SH (eds) Handbook of experimental pharmacology, vol 50, part I. Inflammation. Springer, Berlin Heidelberg New York, pp 464–522
Grigg P, Schaible H-G, Schmidt RF (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, Tegner R (1985) Sensory receptors in ankle joint capsules of normal and arthritic rats. Exp Brain Res 58:29–40
Handwerker HO (1976) Influences of algogenic substances and prostaglandins on the discharges of unmyelinated cutaneous nerve fibres identified as nociceptors. In: Bonica JJ, AlbeFessard DG (eds) Advances in pain research and therapy, vol 1. Raven Press, New York, pp 41–51
Handwerker HO (1976) Pharmacological modulation of the discharge of nociceptive C-fibres. In: Zotterman Y (ed) Sensory functions of the skin in primates. Pergamon Press, Oxford, pp 427–437
Henderson B, Pettipher ER, Higgs GA (1987) Mediators of rheumatoid arthritis. Br Med Bull 43:415–428
Holsapple MP, Schnur M, Yim GKW (1980) Pharmacological modulation of edema mediated by prostaglandin, serotonin and histamine. Agents Actions 10:368–373
Kamakura S, Kamo J, Tsurufuji S (1988) Role of bradykinin in the vascular permeability response induced by carrageenan in rats. Br J Pharmacol 93:739–746
Kanaka R, Schaible H-G, Schmidt RF (1985) Activation of fine articular afferent units by bradykinin. Brain Res 327:81–90
Levine JD, Lau W, Kwiat G, Goetzl EJ (1984) Leukotriene B4 produces hyperalgesia that is dependent on polymorphonuclear leukocytes. Science 225:743–745
Lim RKS (1970) Pain. Annu Rev Physiol 32:269–288
Melmon KL, Webster ME, Goldfinger SE, Seegmiller JE (1967) The presence of a kinin in inflammatory synovial effusion from arthritides of varying etiologies. Arthritis Rheum 10:13–20
Mense S, Meyer H (1988) Bradykinin-induced modulation of the response behaviour of different types of feline group III and IV muscle receptors. J Physiol (Lond) 398:49–63
Moncada S, Ferreira SH, Vane JR (1978) Pain and inflammatory mediators. In: Vane JR, Ferreira SH (eds) Handbook of experimental pharmacology, vol 50, part I. Inflammation. Springer, Berlin Heidelberg New York, pp 588–616
Neugebauer V, Schaible H-G, Schmidt RF (1988) Changes of mechanosensitivity of fine articular afferents by bradykinin alone and by bradykinin in combination with prostaglandin E2. Pflügers Arch 411:R176
Perl ER (1984) Pain and nociception. In: Brookhart JM, Mountcastle VB (eds) Handbook of physiology, section 1. The nervous system, vol III. Sensory processes, part II. American Physiological Society, Bethesda, MD., pp 915–975
Raja SN, Meyer A, Campbell JN (1988) Peripheral mechanims of somatic pain. Anesthesiology 68:571–590
Regoli D (1987) Kinins. Br Med Bull 43:270–284
Salmon JA, Higgs GA (1987) Prostaglandins and leukotrienes as inflammatory mediators. Br Med Bull 43:285–296
Schaible H-G, Schmidt RF (1983) Responses of fine medial articular nerve afferents to passive movements of knee joint. J Neurophysiol 49:1118–1126
Schaible H-G, Schmidt RF (1985) Effects of an experimental arthritis on the sensory properties of fine articular afferent units. J Neurophysiol 54:1109–1122
Schaible H-G, Schmidt RF (1988) Excitation and sensitization of fine articular afferents from cat's knee joint by Prostaglandin E2. J Physiol (Lond) 403:91–104
Schaible H-G, Schmidt RF (1988) Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis. J Neurophysiol 60:2180–2195
Sedgwick AD, Willoughy DA (1985) Initiation of the inflammatory response and its prevention. In: Bonta JL, Bray MA, Parnham MJ (eds) Handbook of inflammation, vol 5. The pharmacology of inflammation. Elsevier, Amsterdam, pp 27–47
Steranka LR, Manning DC, DeHaas CJ, Ferkany JW, Borosky SA, Connor JR, Vavrek RJ, Stewart JM, Snyder SH (1988) Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic action. Proc Natl Acad Sci USA 85:3245–3249
Willis AL (1969) Release of histamine, kinin and prostaglandins during carrageenin-induced inflammation in the rat. In: Montegazza P, Horton EW (eds) Prostaglandins, peptides and amines. Academic Press, New York London, pp 31–38
Woolf AD, Dieppe PA (1987) Mediators of crystal-induced inflammation in the joint. Br Med Bull 43:429–444
Zeitlin JJ, Grennan DM (1976) The role of the inflammatory mediators in joint inflammation. In: Watson BW, Carson DW (eds) Recent advances in rheumatology. Churchill Livingstone, London, pp 195–212
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Neugebauer, V., Schaible, H.G. & Schmidt, R.F. Sensitization of articular afferents to mechanical stimuli by bradykinin. Pflügers Arch 415, 330–335 (1989). https://doi.org/10.1007/BF00370884
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00370884