title: Morphine, the NMDA receptor antagonist MK801 and the tachykinin NK1 receptor antagonist RP67580 attenuate the development of inflammation-induced progressive tactile hypersensitivity.
abstract: Normally-innocuous low-intensity tactile stimuli applied to inflamed tissue induce a progressive decrease in the mechanical flexion withdrawal threshold, the phenomenon of progressive tactile hypersensitivity (PTH). The effects of the mu opioid receptor agonist morphine, the non-competitive NMDA receptor antagonist MK801 and the tachykinin NK1 receptor antagonist RP67580 on the development and maintenance of PTH has now been investigated behaviourally in rats inflamed 48 h earlier by intraplantar complete Freund's adjuvant injection. A standard protocol of eight light tactile stimuli applied to the dorsum of the inflamed paw every 4 s at 5 min intervals resulted, over 60 min, in a 70% fall in mechanical threshold from the pre-conditioning baseline value. Morphine administered before the tactile stimuli at 0.05 mg/kg i.p. had no effect on either baseline thresholds or PTH. At 0.5 mg/kg, morphine prevented the establishment of PTH without changing baseline thresholds. At 5 mg/kg morphine produced analgesia, increasing thresholds above the baseline. MK801 pre-treatment at 0.01 and 0.001 mg/kg i.p. significantly attenuated the development of progressive tactile hyperalgesia without an effect on basal thresholds. RP67580 pre-treatment at 0.1 mg/kg i.p. had no effect, but at both I and 10 mg/kg, attenuated progressive tactile hypersensitivity without changing baseline values. To test the effect of the drugs on established PTH, they were administered 90 min after the commencement of intermittent tactile stimulation to the inflamed hindpaw, when thresholds had reached a plateau. Morphine (0.5 mg/kg) and MK801 (0.01 mg/kg) produced only a small reduction in sensitivity and RP67580 (1 mg/kg) had no effect. These results suggest that the induction of inflammatory progressive tactile hypersensitivity is sensitive to morphine, and to a lesser extent NMDA and NKI receptor antagonists, but these compounds at a dose that do not alter baseline values, do not normalise established tactile hypersensitivity.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK Neuronal Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston MA 02129, USA.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Ma
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Allchorne
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006614:Hindlimb; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000150:complications*; D054833:Isoindoles; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D014110:Touch / Q000502:physiology*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D054833:Isoindoles; D016194:Receptors, N-Methyl-D-Aspartate; D018039:Receptors, Tachykinin; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D016291:Dizocilpine Maleate; D009020:Morphine