Abstract
Inflammatory hyperalgesia is the common denominator of all types of inflammatory pain. Hyperalgesia involves an integrated process that results in the functional up-regulation of the primary sensory neuron. In this circumstance, stimuli which in a normal tissue have little or no effect now activate the nociceptors to induce overt behavioural responses in experimental animals and overt pain in man. Depending upon the inflammatory stimulus and the duration of the plateau of hyperalgesia, the hyperalgesia may be classified as immediate, delayed or persistent. Persistent hyperalgesia is induced by successive daily injections of a hyperalgesic stimulus which causes delayed hyperalgesia. After 6–9 daily injections the sensitivity of the nociceptor does not return to its basal level but, instead, reaches a plateau. If this hyperalgesic plateau is maintained for 7-9 days, by additional daily injections, it persists (in the absence of further injections) for more than thirty days. These observations regarding persistent hyperalgesia indicate an important role for the sensitization of the primary sensory neuron in the establishment of chronic pain and point to the importance of using effective doses of peripherally acting analgesics during the treatment of inflammatory states of long duration. The prevention of a long lasting hyperalgesic state is crucial in order to avoid the development of persistent hyperalgesia. Once the persistent hyperalgesic state is established, cyclo-oxygenase inhibitors are ineffective and the only analgesics able to inhibit the ongoing hyperalgesia are analgesics with other mechanisms of action.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Armstrong, D., Jepson, J.B., Keele, C.A. and Stewart, J.M., Pain producing substance in human inflammatory exsudates and plasma, J. Physiol., 135 (1957) 350–370.
Cunha, F.Q., Lorenzetti, B.B., Poole, S. and Ferreira, S.H., Interleukin 8 as a mediator of sympathetic pain, Br. J. Pharmacol., 104 (1991) 765–767.
Cunha, F.Q., Poole, S., Lorenzetti, B.B. and Ferreira, S.H., The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia, Br. J. Pharmacol., 107 (1992) 660–664.
Donnelly, R.P., Fenton, M.J., Kaufman, J.D. and Gerrard, T.L., IL-1 expression in human monocytes is transcriptionally and postranscriptionally regulated by IL-4, J. Immunol., 146 (1991) 3431–6.
Dray, A., Bettaney, J., Forster, P. and Perkins, M.N., Activation of a bradykinin receptor in peripheral nerve and spinal cord in the neonatal rat in vitro, Br. J. Pharmacol., 1008 (1988) 95.
Ferreira, S.H., Prostaglandins, aspirin-like drugs and analgesia, Nature New Biol., 240 (1972) 200–203.
Ferreira, S.H., Nakamura, M. and Castro, M.S.A., The hyperalgesic effects of prostacyclin and prostaglandin E2., Prostaglandins 16 (1978a) 31–37.
Ferreira, S.H., Lorenzetti, B.B. and Correa, F.M.A., Central and peripheral antialgesic action of aspirin-like drugs, Eur. J. Pharmacol., 53 (1978b) 39–48.
Ferreira, S.H., Are macrophages the body’s alarm cells?, Agents Actions, 10 (1980) 229–230.
Ferreira, S.H., Lorenzetti, B.B., and Rae, G.A., Is methylnalorphinium the prototype of an ideal peripheral analgesic?, Eur. J. Pharmacol., 99 (1984) 23–29.
Ferreira, S.H., Lorenzetti, B.B., Bristow, A.F. and Poole, S., Interleulcin-lp as a potent hyperalgesic agent antagonized by a tripeptide analogue, Nature, 334 (1988) 698–700.
Ferreira, S.H., Lorenzetti, B.B., and Campos, D.I., Induction, inhibition and restoration of a persistent hypersensitive state, Pain, 42 (1990) 365–371
Ferreira, S.H. and Lorenzetti, B.B., Glutamate spinal retrogade sensitization of primary sensory neurons associated with nociception, Neuropharmacology, 33 (1994) 1479–1485.
Handwerker, H.O. and Reeh, P.W., Pain and Inflammation. In: M.R. Bond, J.E. Charlton and C.J. Woolf (Eds.), Proceedings of the Vlth World Congress on Pain, Elsevier Science, Amsterdam, 1991, pp. 59–70.
Lang, E., Novak, A., Reeh, P.W. and Handwerker, H.O., Chemosensitivity of fine afferents from rat skin in vitro, J. Neurophysiol., 63 (1990) 887–901.
Lorenzetti, B.B. and Ferreira, S.H., Mode of analgesic action of dipyrone: Direct antagonism of inflammatory hyperalgesia, Eur. J. Pharmacol., 114 (1985) 375–381.
Lorenzetti, B.B. and Ferreira, S.H, Activation of the arginine-nitric oxide pathway in primary sensory neurons contributes to dipyrone-induced spinal and peripheral analgesia, Inflamm. Res., 45 (1996) 308–311.
McMahon, S.B. and Koltzenburg, M., Novel classes of nociceptors: beyond Sherrington, TINS, 13 (1990) 199–201.
Nakamura, M. and Ferreira, S.H., A peripheral sympathetic component in inflammatory hyperalgesia, Eur. J. Pharmacol., 135 (1987) 145–153.
Niiro, H., Otsuka, T., Tanabe, T., Hara, S., Kuga, S., Nemoto, Y., Tanaka, Y., Nakashima, H., Kitajima, S., Abe, M., et al., Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: its underlying mechanism in comparison with interleukin-4, Blood, 85 (1995) 3736–45.
Randall, L.O. and Selitto, J.J., A method for measurement of analgesic activity on inflamed tissue, Arch. Int. Pharmacodyn. Ther., 111 (1957) 409.
Sicuteri, F., Franciullacci, F., Franchi, G. and Del Bianco, P.L., Serotonin-bradykinin potentiation on the pain receptors in man, Life Sci., 4 (1965) 309–316.
Smith, J.A.M., Amagasu, S.M., Eglen, R.M., Hunter, J.C. and Bley, K.R., Characterization of prostanoid receptor-evoked responses in rat sensory neurones, Br. J. Pharmacol., 124 (1998a) 513–523.
Smith, J.A.M., Amagasu, S.M., Eglen, R.M., Hunter, J.C. and Bley, K.R., Characterization of the arachidonic acid metabolites mediating bradykinin and noradrenaline hyperalgesia, Brain Res., 458 (1998b) 402–406.
Steranka, I..R., Manning, D.C. and Dehass, C.J., Bradykinin as pain mediator: receptors are localized to sensory neurons and antagonists have analgesic actions, Proc. Natl. Acad. Sci. USA, 85 (1988) 3245–3249.
Tonussi, C.R. and Ferreira, S.H., Rat knee joint carrageenin incapacitation test: an objective screen for central and peripheral analgesics, Pain, 48 (1992) 421–427.
Tonussi, C.R. and Ferreira, S.H., Mechanism of diclofenac analgesia: direct inhibition of inflammatory sensitization, Eur. J. Pharmacol., 251 (1994) 173–179.
Tonussi, C.R. and Ferreira, S.H., Bradykinin-induced knee joint incapacitation involves bradykinin B2 receptor mediated hyperalgesia and bradykinin B1 receptor-mediated nociception, Eur J Pharmacol., 326 (1997) 61–5.
Wang, P., Wu, P., Siegel, M.I., Egan, R.W. and Billah, M.M., Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms, J. Biol. Chem., 270 (1995) 9558–63.
Whalley, E.T., Clegg, S., Stewart, J.M. and Vavrek, R.J., The effect of kinin agonists and antagonists on the pain response of the human blister base, Naunyn-Schmiedebergs Arch. Pharmacol., 336 (1987) 652–655.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media New York
About this chapter
Cite this chapter
Ferreira, S.H., Sachs, D., Cunha, F.Q., Lorenzetti, B.B. (2000). Persistent Hyperalgesia and Cytokines. In: Saadé, N.E., Apkarian, A.V., Jabbur, S.J. (eds) Pain and Neuroimmune Interactions. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4225-4_1
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4225-4_1
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6897-7
Online ISBN: 978-1-4615-4225-4
eBook Packages: Springer Book Archive