Sensitisation of group III articular afferents to mechanical stimuli by substance P

To examine the excitatory and sensitising effects of substance P (SP) on articular afferents in normal and acutely inflamed cat knee joints.

In anesthetised cats recordings were made from 15 group III (conduction velocity 2.5-20 m/s) and 25 group IV afferent units (conduction velocity < 2.5 m/s) of the medial articular nerve of normal and acutely inflamed knee joints. SP (10 and 100 microg) was administered close-arterially.

SP at doses of 10 microg and 100 microg activated less than 50% of both group III and group IV units. The proportion of SP-positive units was significantly higher in inflamed (10 of 21) than in normal joints (2 of 18). SP induced activity in initially silent units or increased ongoing activity after latencies varying from 2 s to 5 min. The SP-evoked activity had an irregular pattern, a variable duration, and was not related to the dose injected. Bolus injections of SP (100 microg) sensitised group III articular afferents but not group IV units to noxious movements of the joint, regardless whether the units were from normal or acutely inflamed joints. The responses to innocuous movements were not influenced by SP. Group III units, initially not activated by any movement, displayed vigorous discharges to noxious movements after close-arterial SP. In 3 group III units tested, the SP-induced augmentation of responses to noxious movements was not mimicked by close-arterial injection of histamine (3.3 microg).

It is concluded that SP contributes to the sensitisation of a subpopulation of high-threshold articular afferents. Thus this neuronal mediator released peripherally in response to an injury or acute inflammation causes considerable changes in the mechanosensitivity of this subpopulation of nociceptive joint afferents.