Effect of capsaicin on voltage-gated currents of trigeminal neurones in cell culture and slice preparations

Effects of capsaicin on voltage-gated currents were examinedin vitro by whole-cell patch-clamp recordings from small neurones of rat trigeminal ganglia either in slice preparations or in different cell cultures. Cells were classified as sensitive to capsaicin if they responded with inward current and/or conductance change to the agent in nanomolar concentration. Capsaicin (150 to 330 nM) in sensitive cells reduced the mixed inward current evoked by depolarizing step or ramp commands in all preparations. In cultured cells, the inward current was depressed to 32.78±26.42% (n = 27) of the control. Both the tetrodotoxin-sensitive and -resistant inward currents were affected. The data support the concept that capsaicin besides acting on VR-1 receptors inhibits also some voltage gated channels. In 34 cultured cells, capsaicin increased the slope conductance to 170.5±68%. Percentage of capsaicin sensitive cells observed in nerve growth factor-treated cultured cell populations was higher (77.8%) than in the two other preparations (14.3 or 38.8%). It is concluded that 1) depression of the voltage-gated currents may play an important role in the functional desensitization of the sensory receptors and in the analgesic effect induced by the agent and 2) cell body of sensory neurones under native condition seems less sensitive to capsaicin then that of cells cultured in the presence of nerve growth factor

Impaired capsaicin-induced decrease in heart rate and coronary flow in isolated heart of diabetic rats

The effect of capsaicin (0.1μM) on heart rate and coronary flow was studied in Langendorff-perfused heart from streptozotocin-induced (50 mg/kg i.v.) diabetic rats where sensory neuropathy developed. In hearts from animals 4- and 8-week diabetes baseline heart rate and coronary flow decreased from 317.9±2.9 b.p.m. and 13.4±0.7 ml/min to 255.1±12.7 and 219.8±2.8 b.p.m. and 8.9±0.6 and 10.0±0.1 ml/min (P<0.05), respectively. Capsaicin significantly decreased both variables in either normal or 4-week diabetic animals its effects, however, on coronary flow or heart rate were missing in preparations from 8-week diabetic rats. Endothelin-1 (0.1 nM), the putative mediator of the capsaicin effect, significantly decreased heart rate and coronary flow irrespective of the presence or absence of diabetes. In the femoral nerve of streptozotocin-treated animals conduction velocity involving both fast conducting A- and slow-conducting C-fibres was decreased proportional to the duration of the pre-existing diabetic state. It is concluded that in insulin deficient diabetes the diminished responses evoked by capsaicin on heart rate and coronary flow are signs of sensory neuropathy. This is related to a feeble endothelin release from sensory nerve endings without changes in post-receptor mechanisms mediating the endothelin effects

Selective responsiveness of polymodal nociceptors of the rabbit ear to capsaicin, bradykinin and ultra-violet irradiation.

1. The activity of single C- and A-fibre cutaneous sensory units was recorded from the great auricular nerve of anaesthetized rabbits to compare the effects of chemical with other forms of stimulation under several experimental conditions. Chemical agents were delivered by close arterial injection. 2. Small intra-arterial injections of bradykinin (0.2 microgram) and a substantial range of capsaicin doses (2-200 micrograms) consistently activated C polymodal nociceptors without exciting other types of C- or A-fibre cutaneous sense organs. 3. Topical application of xylene to the receptive field of polymodal nociceptors evoked a strong excitation which lasted several minutes. 4. The responses of polymodal nociceptors to mechanical, chemical (bradykinin, xylene) and noxious thermal stimuli were suppressed or abolished after large intra-arterial doses of capsaicin. Capsaicin desensitization of polymodal nociceptors to one kind of stimulation often was not paralleled by similar changes in responsiveness to other stimuli. However, on the average, capsaicin desensitization altered responses to thermal, chemical and mechanical stimuli without afferent selectivity. 5. Background discharge developed in C polymodal nociceptors of the rabbit ear following ultra-violet irradiation sufficient to produce evidence of delayed inflammation. Noxious heat and bradykinin injection (0.2 micrograms) evoked more activity from C polymodal nociceptors in the irradiated ears than from control units