Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuvant arthritis.

1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivalent to 50 mg kg-1 aspirin) both caused a maximal reduction of about 40% in mechanically-evoked discharge and of 30% in ongoing (spontaneous) activity by about 15 min after the injection: a second dose of either drug did not have any significant additional effect on discharge. 3. The prostanoid IP receptor agonist, cicaprost (0.1-0.5 micrograms), increased both mechanically-evoked and ongoing discharge to pre-paracetamol levels when injected close-arterially 30-50 min after paracetamol, whereas prostaglandin E2 (PGE2) was relatively ineffective at restoring activity. 4. The results suggest that prostacyclin (PGI2) contributes to the sensitization of high-threshold joint mechanonociceptors in adjuvant-induced monoarthritis, and that paracetamol and L-AS both act to reduce discharge by inhibiting the synthesis of prostacyclin in the joint capsule. 5. Paracetamol has a direct peripheral action affecting joint capsule mechanonociceptors in rat adjuvant-induced arthritis which is very similar to that of the soluble aspirin preparation, L-AS. These findings, together with the existing literature concerning the anti-arthritic effects of paracetamol, are relevant to the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

The effect of lysine acetylsalicylate on joint capsule mechanoreceptors in rats with polyarthritis.

Joint capsule mechanoreceptors in arthritic rats are more sensitive to pressure than similar receptors in normal animals. This greater sensitivity was reversed by the intravenous or topical administration of lysine acetylsalicylate in anaesthetised rats in doses of 15 to 50 mgm ASA-equivalent/kg. The reduction in sensitivity began within 5-10 min and reached a minimum mean value of 35% of the control after 35 to 40 min. During this period there was a negative linear or exponential relation between the amplitude of response to a controlled mechanical stimulus and time after administration of lysine acetylsalicylate. Control values of sensitivity were reached about 65-70 min following treatment with lysine acetylsalicylate. The results are interpreted as indicating that the high sensitivity of the arthritic joint capsule receptors is due to locally produced prostaglandins, such as prostacyclin.

The physiological interpretation of electrical stimulation of the nervous system.

The physiological basis of the responses of cells in the nervous system to electrical stimulation is described by reference to the strength-duration curve and to the characteristics of ion-carriers in the cell membranes. The effects of the electrode systems used to deliver the electrical stimuli are considered briefly, followed by an account of the relative electrical excitability of nervous elements in peripheral nerves, spinal cord and the cellular nuclei of the nervous system. The responses of more complex physiological systems to both peripheral and central electrical stimulation are then considered, with more detailed reference to neural mechanisms involved in analgesia at peripheral, spinal and brain-stem levels.