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The role of PGE2 in the sensitization of mechanoreceptors in normal and inflamed ankle joints of the rat

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Summary

The role of PGE2 in the sensitization of highthreshold tarsal joint mechanoreceptors (putative nociceptors) has been investigated in 11 arthritic and 16 normal rats. Injections of a low dose of Freund's complete adjuvant at multiple sites into the tissues surrounding the ankle joint induced a chronic unilateral monoarthritis in the injected limb. Measurements of both spontaneous activity and responses of tarsal joint mechanoreceptors to repeated graded mechanical stimuli were made. All of the mechanoreceptors examined had afferent fibres with conduction velocities in the C or A-δ range. Using this new model of joint inflammation we have shown that lysine acetylsalicylate reduces the mechanical sensitivity of these joint mechanoreceptors and reduces the spontaneous activity in afferent nerve fibres. Prostaglandin E2 is unable to restore either the spontaneous activity in the afferent axon or the mechanical sensitivity of tarsal joint mechanoreceptors after lysine acetylsalicylate in the arthritic rat. Similarly, PGE2 does not sensitize or excite tarsal joint mechanoreceptors in the normal rat. In the normal rat, however, PGE2 potentiates the excitatory action of bradykinin and enhances the sensitizing effect of bradykinin on the responses of joint mechanoreceptors to mechanical stimulation when both substances are injected simultaneously. These results indicate that PGE2 is not important in the sensitization of these joint mechanoreceptors in this model of chronic joint inflammation but that in other circumstances PGE2 may be able to contribute to a sensitization of joint mechanoreceptors by enhancing the action of bradykinin.

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References

  • Beck PW, Handwerker HO (1974) Bradykinin and serotonin effects on various types of cutaneous nerve fibres. Pflügers Arch 347: 209–222

    Google Scholar 

  • Billingham MEJ, Davies GE (1979) Experimental models of arthritis in animals as screening tests for drugs to treat arthritis in man. Handbook Exp Pharmacol 50: 108–144

    Google Scholar 

  • Birrell GJ, Grubb BD, Iggo A, McQueen DS (1990). Actions of PGE2 and cicaprost on the sensitivity of high-threshold mechanoreceptors in normal and inflamed ankle joints of the anaesthetised rat. J Physiol 420: 33P

  • Blair IA MacDermot J (1981) The binding of [3H]-prostacyclin to membranes of a neuronal somatic hybrid. Br J Pharmacol 72: 435–441

    Google Scholar 

  • Bombardieri S, Cattani P, Ciabattoni G, Di Munno O, Pasero G, Patrono C, Pinca E, Pugliese F (1981) The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and non-steroidal anti-inflammatory drugs. Br J Pharmacol 73: 893–901

    Google Scholar 

  • Chahl LA, Iggo A (1977) The effects of bradykinin and prostaglandin E1 on rat cutaneous afferent nerve activity. Br J Pharmacol 59: 343–347

    Google Scholar 

  • Coleman RA, Humphrey PPA, Kennedy I, Lumley P (1984) Prostanoid receptors-the development of a working classification. Trends Pharmacol Sci 5: 303–306

    Google Scholar 

  • Egg D, Gunther R, Herold M, Kerschbaumer F (1980) Prostaglandin E2 und 392–01-Konzentrationen in der Synovia bei rheumatischen und traumatischen Kniegelenkerkrankungen. Z Rheumatol 39: 170–175

    Google Scholar 

  • Ferreira SH (1972) Prostaglandins, aspirin-like drugs and analgesia. Nature 240: 200–203

    Google Scholar 

  • Franz M, Mense S (1975) Muscle receptors with group IV afferent fibres responding to application of bradykinin. Brain Res 92: 369–383

    Google Scholar 

  • Guilbaud G, Iggo A (1985) The effect of lysine acetylsalicylate on joint capsule mechanoreceptors in rats with polyarthritis. Exp Brain Res 61: 164–168

    Google Scholar 

  • Guilbaud G, Iggo, A, Tegner R (1985) Sensory receptors in ankle joint capsules of normal and anthritic rats. Exp Brain Res 58: 29–40

    Google Scholar 

  • Grubb BD, McQueen DS, Iggo A, Birrell GJ, Dutia MB (1988) A study of 5-HT receptors associated with afferent nerves located in normal and inflamed rat ankle joints. Agents Actions 25:216–218

    Google Scholar 

  • Heppelmann B, Pfeffer A, Schaible H-G, Schmidt RF (1986) Effects of acetylsalicyclic acid and indomethacin on single groups III and IV sensory units from acutely inflamed joints. Pain 26: 337–351

    Google Scholar 

  • Higgs GA, Vane JR, Hart FD, Wojtuleweski JA (1974) Effects of anti-inflammatory drugs on prostaglandins in rheumatoid arthritis. In: Robinson HJ, Vane JR (eds). Prostaglandin synthetase inhibitors. Raven Press, New York, pp 165–173

    Google Scholar 

  • Iadarola MJ, Douglass J, Civelli O, Naranjo JR (1988) Differential activation of spinal cord dynorphin and enkephalin neurones during hyperalgesia: evidence using cDNA hybridisation. Brain Res 455: 205–212

    Google Scholar 

  • Kanaka R, Schaible H-G, Schmidt RF (1985) Activation of fine articular afferent units by bradykinin. Brain Res 327: 81–90

    Google Scholar 

  • Kniffki K-D, Mense S, Schmidt RF (1978) Responses of group IV afferent units from skeletal muscle to stretch, contraction and chemical stimulation. Exp Brain Res 31: 511–522

    Google Scholar 

  • Kumazawa T, Mizumura K (1977) Thin-fibre receptors responding to mechanical, chemical and thermal stimulation in the skeletal muscle of the dog. J Physiol 273: 179–194

    Google Scholar 

  • Martin HA, Basbaum AI, Kwiat GC, Goetzel EJ, Levine JD (1987) Leukotriene and prostaglandin sensitization of cutaneous high threshold C and A-delta mechanonociceptors in the hairy skin of rat hind-limbs. Neurosci 22: 651–659

    Google Scholar 

  • McQueen DS, Iggo DS, Birrell GJ, Grubb BD (1990) Effects of aspirin and paracetamol on high-threshold tarsal joint mechano receptors in anaesthetised rats with adjuvant-induced arthritis. J Physiol 425: 35P

  • 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

    Google Scholar 

  • Mense S (1977) Nervous outflow from skeletal muscle following chemical noxious stimulation. J Physiol 267: 75–88

    Google Scholar 

  • Millan MJ, Czlonkowski A, Morris B, Stein C, Arendt R, Huber A, Höllt V, Herz A (1988) Inflammation of the hind limb as a model of unilateral, localised pain: influence on multiple opioid systems in the spinal cord of the rat. Pain 35: 299–312

    Google Scholar 

  • Moncada S, Ferreira SH, Vane JR (1975) Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint. Eur J Pharmacol 31: 250–260

    Google Scholar 

  • Neugebauer V, Schaible H-G, Schmidt RF (1989) Sensitization of articular afferents to mechanical stimuli by bradykinin. Pflügers Arch 415: 330–335

    Google Scholar 

  • Newbould BB (1963) Chemotherapy of arthritis induced in rats by injection of mycobacterial adjuvant. Br J Pharmacol 21: 127–136

    Google Scholar 

  • Schaible H-G, Schmidt RF (1988) Excitation and sensitization of fine articular afferents from cat's knee joint by prostaglandin E2. J Physiol 403: 91–104

    Google Scholar 

  • Sedgewick AD, Willoughby, DA (1985) Initiation of the inflammatory response and its prevention. In: Bonta IL, Bray MA, Parnham MJ (eds) The pharmacology of inflammation, Vol 5. Elsevier Scientific Publ BV, Amsterdam, pp 27–47

    Google Scholar 

  • Stein C, Millan MJ, Shippenberg TS, Herz A (1988) Peripheral effect of fentanyl upon nociception in inflamed tissue of the rat. Neurosci Lett 84: 225–228

    Google Scholar 

  • Trang LE, Ganström E, Lövgren O (1977) Levels of prostaglandins F392–02 and E2 and thromboxane B2 in joint fluid in rheumatoid arthritis. Scand J Rheumatol 6: 151–154

    Google Scholar 

  • Weihe E, Millan MJ, Höllt V, Nohr D, Herz A (1989) Induction of the gene encoding pro-dynorphin by experimentally induced arthritis enhances staining for dynorphin in the spinal cord of rats. Neurosci 31: 77–95

    Google Scholar 

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Grubb, B.D., Birrell, G.J., McQueen, D.S. et al. The role of PGE2 in the sensitization of mechanoreceptors in normal and inflamed ankle joints of the rat. Exp Brain Res 84, 383–392 (1991). https://doi.org/10.1007/BF00231460

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  • DOI: https://doi.org/10.1007/BF00231460

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