The effects of 5-HT on articular sensory receptors in normal and arthritic rats.
1. The effects of intra arterial (i.a.) injections of 5-hydroxytryptamine (5-HT, 1-100 micrograms) on the discharge of (a) identified articular high threshold mechanoreceptors and (b) unidentified chemosensitive receptors in the ankle joint have been studied electrophysiologically in anaesthetized normal and arthritic rats. Recordings were made from a fine branch of the medial plantar nerve. 2. 5-HT increased the mechanical responsiveness of high threshold nociceptive mechanoreceptors with C and A delta fibre afferents in both normal and adjuvant-arthritic rats. Receptors in arthritic joints were more sensitive to 5-HT than were those from normal joints. 3. 5-HT produced a complex response from both types of articular receptors following i.a. injection. Two separate components were identified: (a) a fast transient burst of activity was obtained within 10 s of this injection in 66% of units from normal animals and 45% from arthritics, followed by (b) a delayed slow longer-lasting excitation seen in 62% of the units examined from normals and 77% of units from arthritic rats. 4. Increased mechanoreceptor responsiveness produced by 5-HT was reduced or abolished by the 5-HT3 receptor antagonists studied (MDL 72222, ICS 205-930, or GR 38032F, in single doses of 100 micrograms kg-1, i.a.). 5. Fast excitation showed marked tachyphylaxis and was antagonized by MDL 72222, ICS 205-930 or GR 38032F. It was unaffected by ketanserin (100 micrograms kg-1, i.a.). Delayed excitation was reduced or abolished by ketanserin but was unaffected by the 5-HT3-receptor antagonists. 6. Administration of MDL 72222, ICS 205-930 or GR 38032F caused short lasting (< 5 min) reductions in background activity from both types of unit recorded in arthritic rats, as well as in normal rats in which activity had increased following administration of 5-HT. Ketanserin caused similar reductions in background activity in chemosensitive units, but had no effect on mechanoreceptors. 7. At least two types of receptor are involved in the actions of 5-HT on articular sensory receptors with fine afferent fibres. Increased mechano-responsiveness involves a 5-HT3-receptor as does fast excitation. Delayed excitation probably involves a 5-HT2-receptor. Endogenous 5-HT appears not to play a crucial role in sensitization of high threshold mechanoreceptors in this model of chronic inflammation and arthritis, although its local release may potentiate the actions of other inflammatory mediators on sensory receptors in the ankle joint.
Birrell
G J
GJ
Department of Pharmacology, University of Edinburgh Medical School.
McQueen
D S
DS
Iggo
A
A
Grubb
B D
BD
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D007596:Joints / Q000187:drug effects / Q000294:innervation*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology; D012702:Serotonin Antagonists; D014326:Tropanes / Q000494:pharmacology
D012702:Serotonin Antagonists; D014326:Tropanes; D012701:Serotonin; C042253:bemesetron