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Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat.

Abstract

BACKGROUND

These studies were undertaken to investigate the site and nature of the antinociceptive effect of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and paracetamol in the central nervous system (CNS).

METHODS

Different nociceptive test models were employed: the tail-flick and hot-plate tests (thermoreceptors), the writhing test (visceral chemoreceptors) the "scratching, biting, licking" (SBL) behaviour and the colorectal distension test (mechanoreceptors). Drugs were given intraperitoneally (i.p.), intracerebroventricularly (i.c.v.), intrathecally (i.t.) or as local injection via cannulae implanted stereotactically. Nerve destruction was made by local injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Whole brain and spinal cord contents of serotonin and 5-hydroxyindole acetic acid (5-HIAA) were analysed by high pressure liquid chromatography (HPLC).

RESULTS

Injections of diclofenac induced antinociception in visceral pain models (writhing test, colorectal distension test), but not in two models of somatosensory pain (tail-flick and hot-plate test). The antinociceptive effect of diclofenac (i.p., i.c.v., or i.t.) was reversed by i.p. naloxone. Naloxone also reversed the effect of diclofenac injected locally into thalamic and hypothalamic areas involved in pain transmission as well as in n. paragigantocellularis or n. raphe magnus. In addition, chemical destruction of the n. raphe region attenuated the antinociceptive effect of diclofenac. Inhibition of serotonergic transmission by pretreatment with methiothepin, ritanserin, parachlorophenylalanine (PCPA) or 5,7-DHT also reduced the antinociceptive effect of diclofenac in a visceral pain model. Pretreatment with diclofenac or ibuprofen blocked pain behaviour (SBL) after activation of excitatory amino acid receptors of the NMDA type, but not pain behaviour after activation of AMPA or substance P (SP) receptors. Paracetamol inhibited hyperalgesia after both NMDA and SP. The antinociceptive effects of diclofenac, ibuprofen and paracetamol were reversed by L-arginine, but not by D-arginine.

CONCLUSIONS

The antinociceptive effect of diclofenac involves a central nervous component which may be elicited from several defined areas in the CNS. Part of the antinociceptive effect seems to be mediated by descending inhibitory opioid, serotonin and/or other neurotransmitter systems interfering with visceral pain impulse traffic at the spinal level. NSAIDs and paracetamol interfere with nociception associated with spinal NMDA receptor activation. This effect involves an inhibitory action on spinal nitric oxide (NO) mechanisms. Possibly, the supraspinal antinociceptive effect of NSAIDs may be explained by an analogous action.

Authors+Show Affiliations

Department of Pharmacology, University of Gothenburg, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

7725891

Citation

Björkman, R. "Central Antinociceptive Effects of Non-steroidal Anti-inflammatory Drugs and Paracetamol. Experimental Studies in the Rat." Acta Anaesthesiologica Scandinavica. Supplementum, vol. 103, 1995, pp. 1-44.
Björkman R. Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat. Acta Anaesthesiol Scand Suppl. 1995;103:1-44.
Björkman, R. (1995). Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat. Acta Anaesthesiologica Scandinavica. Supplementum, 103, 1-44.
Björkman R. Central Antinociceptive Effects of Non-steroidal Anti-inflammatory Drugs and Paracetamol. Experimental Studies in the Rat. Acta Anaesthesiol Scand Suppl. 1995;103:1-44. PubMed PMID: 7725891.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat. A1 - Björkman,R, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 1 EP - 44 JF - Acta anaesthesiologica Scandinavica. Supplementum JO - Acta Anaesthesiol Scand Suppl VL - 103 N2 - BACKGROUND: These studies were undertaken to investigate the site and nature of the antinociceptive effect of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and paracetamol in the central nervous system (CNS). METHODS: Different nociceptive test models were employed: the tail-flick and hot-plate tests (thermoreceptors), the writhing test (visceral chemoreceptors) the "scratching, biting, licking" (SBL) behaviour and the colorectal distension test (mechanoreceptors). Drugs were given intraperitoneally (i.p.), intracerebroventricularly (i.c.v.), intrathecally (i.t.) or as local injection via cannulae implanted stereotactically. Nerve destruction was made by local injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Whole brain and spinal cord contents of serotonin and 5-hydroxyindole acetic acid (5-HIAA) were analysed by high pressure liquid chromatography (HPLC). RESULTS: Injections of diclofenac induced antinociception in visceral pain models (writhing test, colorectal distension test), but not in two models of somatosensory pain (tail-flick and hot-plate test). The antinociceptive effect of diclofenac (i.p., i.c.v., or i.t.) was reversed by i.p. naloxone. Naloxone also reversed the effect of diclofenac injected locally into thalamic and hypothalamic areas involved in pain transmission as well as in n. paragigantocellularis or n. raphe magnus. In addition, chemical destruction of the n. raphe region attenuated the antinociceptive effect of diclofenac. Inhibition of serotonergic transmission by pretreatment with methiothepin, ritanserin, parachlorophenylalanine (PCPA) or 5,7-DHT also reduced the antinociceptive effect of diclofenac in a visceral pain model. Pretreatment with diclofenac or ibuprofen blocked pain behaviour (SBL) after activation of excitatory amino acid receptors of the NMDA type, but not pain behaviour after activation of AMPA or substance P (SP) receptors. Paracetamol inhibited hyperalgesia after both NMDA and SP. The antinociceptive effects of diclofenac, ibuprofen and paracetamol were reversed by L-arginine, but not by D-arginine. CONCLUSIONS: The antinociceptive effect of diclofenac involves a central nervous component which may be elicited from several defined areas in the CNS. Part of the antinociceptive effect seems to be mediated by descending inhibitory opioid, serotonin and/or other neurotransmitter systems interfering with visceral pain impulse traffic at the spinal level. NSAIDs and paracetamol interfere with nociception associated with spinal NMDA receptor activation. This effect involves an inhibitory action on spinal nitric oxide (NO) mechanisms. Possibly, the supraspinal antinociceptive effect of NSAIDs may be explained by an analogous action. SN - 0515-2720 UR - https://www.unboundmedicine.com/medline/citation/7725891/Central_antinociceptive_effects_of_non_steroidal_anti_inflammatory_drugs_and_paracetamol__Experimental_studies_in_the_rat_ L2 - https://www.lens.org/lens/search/patent/list?q=citation_id:7725891 DB - PRIME DP - Unbound Medicine ER -