Effects of neonatal capsaicin treatment and streptozotocin-induced diabetes on urinary bladder function in rats

A significant increase in the size and weight of the urinary bladder was observed 2 weeks after streptozotocin treatment and 2 months after neonatal capsaicin treatment. Both treatments induced a significant increase in the level of [³H]quinuclidinyl benzilate binding to muscarinic cholinergic receptors in the urinary bladder membranes. However, contractile responses of urinary bladder muscle strips to carbachol (0.3–20 μM) were not significantly affected by either treatment. On the other hand, neonatal capsaicin treatment, but not streptozotocin treatment, significantly enhanced contractile responses of bladder strips to electric field stimulation.     

The receptive part of the primary afferent axon is most vulnerable to systemic capsaicin in adult rats

The present study shows that systemic capsaicin in adult rats results in a significant loss of axons in the subepidermal nerve plexus of the posterior leg but no loss of axons in the sural nerves of these same animals. These data are interpreted as indicating that the receptive part of the peripheral sensory axon is destroyed but that the cell body and most of the peripheral axon remains intact. Thus we suggest that the receptive part of the peripheral sensory axon is the most vulnerable part of the primary afferent neuron to capsaicin in these animals. These findings may explain the observation that adult rats treated with systemic capsaicin are deficient in their responses to certain painful stimuli but usually do not show obvious signs of primary afferent neuron death. We also suggest that as the dose of capsaicin is increased the whole neuron dies. It remains to be determined if the peripheral damage reported here is related to the striking loss of primary afferent markers in the dorsal horn that is also seen after this treatment.     

Cellular mechanism of action of resiniferatoxin: a potent sensory neuron excitotoxin

The mechanism of activation of sensory neurons by the potent irritant resiniferatoxin (RTX) was compared with that of the pungent compound, capsaicin. RTX and capsaicin evoked an inward, depolarising current associated with an increase in membrane conductance in a subpopulation of dissociated cultured neurons from rat dorsal root ganglia. RTX also evoked an uptake of⁴⁵Ca into and an efflux of [¹⁴C]guanidinium and of⁸⁶Rb from these cells but was at least 100-fold potent than capsaicin. The levels of cGMP, but not cAMP were elevated by RTX. Prolonged exposure to RTX damaged DRG neurons by a predominantly osmotic process. RTX-sensitive cells were identified by a cobalt-staining method; neurofilament-containing DRG neurons were RTX-insensitive as were all sympathetic neurons and non-neuronal cells. Cultured DRG neurons from chick embryos were also unaffected by RTX. In a neonatal rat spinal cord-tail preparation in vitro, RTX activated capsaicin-sensitive peripheral noiciceptive fibres and caused a subsequent spinal cord depolarization measured in the ventral spinal roots. Neither prolonged exposure to a phorbol ester, to desensitize/down-regulate protein kinase C, nor inhibition of protein kinase C by staurosporine affected responses produced by RTX or capsaicin. The effects of capsaicin were abolished when preparations were exposed to desensitizing concentrations of RTX. RTX therefore acts as a highly potent capsaicin analogue to activate a subpopulation of rat sensory neurons.     

辣椒素致眼化学伤28例临床观察

目的观察辣椒素致眼化学伤的临床特征及治疗效果。方法回顾性分析28例（43只眼）辣椒素致眼化学伤病例的临床表现、治疗及疾病转归。结果辣椒素对眼部损伤多局限于眼表，虽然预后较好，但部分病例症状较重、角膜上皮层愈合迟缓。经反复结膜囊冲洗、控制局部炎性反应、预防感染、促进角膜上皮修复等积极治疗后，本组病例均治愈，平均病程（9．37±4．91）d（4～28d）。除1侧假性胬肉外，束发现其他眼化学伤并发症。结论辣椒素催泪喷射器可致I度眼化学伤。主要发病机制是辣椒素激活瞬时感受器电位香草酸受体1（transient receptor potential vanilloid 1, TRPV1 ）后释放P物质（substanceP，SP）介导的局部炎性反应。常规治疗眼化学伤的方法和药物对本病有效。     

Hyperalgesia to heat after intradermal injection of capsaicin

Capsaicin injected intradermally into the human forearm lowered the pain threshold for heat at the injection site. Both the magnitude and duration of hyperalgesia were dose dependent over the range of 0.1-100 micrograms, given in a constant volume of 10 microliter. Thus, capsaicin may be a useful tool in studies of the neural mechanisms of hyperalgesia.     

Viscero‐somatic reflexes in referred pain areas evoked by capsaicin stimulation of the human gut

The interaction between visceral pain and the sympathetic nervous system is only sparsely investigated in quantitative human studies. Referred visceral pain can be evoked experimentally by application of substances such as capsaicin (the pungent substance of chilli pepper) to the gut. The aim of the present study was to induce referred visceral pain from the small and large intestine in 32 volunteers via the stomal opening in patients with ileo‐ or colostomy and quantify the viscero‐somatic reflex responses in these referred pain areas by thermography and laser doppler flowmetry. Capsaicin evoked pain and referred pain areas in all subjects. In the referred pain area, the temperature increased by approximately 0.6°C (P<0.001) and the blood flow by approximately 35AU (P<0.001). Saline was used in a control experiment, and no temperature and blood flow changes were found. The present quantitative human study of viscero‐somatic reflexes showed dramatic sympathetic responses in the referred pain areas after experimentally induced gut pain.     

Analgesic activities of spinal cord substance P antagonists implicate substance P as a neurotransmitter of pain sensation

Substance P (SP) injected into intraspinal (i.s.) spaces caused mice to vigorously scratch and bite their skins in an apparent reaction to a perceived cutaneous sensation. The scratching behavior was similar to the reciprocal hindlimb-scratching syndrome (RHS) described for intracranial (i.c.) SP injections. Radiotracer experiments, as well as potency and latency measurements, demonstrated that SP-induced scratching, whether induced by the i.c. or i.s. route, was due to SP receptor stimulation in the cervicothoracic cord. Similarly, biting was due to SP stimulation of the lumbosacral spinal cord. Mice coated with capsaicin, an irritant chemical, scratched and bit the coated areas in a manner similar to animals injected with i.s. SP. Standard analgesics depressed this scratching behavior elicited by topical capsaicin. Non-analgesic drugs, with the exception of amphetamine, did not affect capsaicin-induced pain. It is concluded that i.s. SP induces a painful sensory experience. Some piperazinone derivatives of substance P's C-terminal hexapeptide are shown to specifically antagonize the scratching induced by i.s. SP with little or no effect on motor behavior. These antagonists depressed scratching elicited by topical capsaicin and were analgesic on the hot-plate test. It is concluded that SP is a natural neurotransmitter for pain and that antagonism of endogenous SP systems causes analgesia.     

The influence of capsaicin sensitive neurons on stress-induced release of ACTH

Changes in the plasma levels of ACTH in response to cold exposure or restraint stress were measured in adult rats which had been pretreated with capsaicin or vehicle as neonates. There was no difference in basal ACTH levels between capsaicin and vehicle pretreated animals. Following restraint stress, ACTH levels rose similarly in vehicle and capsaicin pretreated rats, indicating that the pituitary-adrenal system is not impaired by capsaicin pretreatment. However, following cold exposure ACTH levels rose only in control animals whereas no change was observed in capsaicin pretreated animals. It is concluded that capsaicin-sensitive afferent neurons participate in the cold stress-induced increase of plasma ACTH levels.     

A double-blind placebo-controlled trial of intranasal capsaicin for cluster headache

It has been suggested that treatment of cluster headache (CH) patients with topical capsaicin may desensitize sensory neurons by depleting the nerve terminals of substance P. We attempted to determine whether capsaicin is effective in aborting CH attacks. Patients in acute cluster were randomized to receive either capsaicin or placebo in the ipsilateral nostril for 7 days. Patients recorded the severity of each headache for 15 days. Headaches on days 8–15 of the study were significantly less severe in the capsaicin group vs the placebo group. There was also a significant decrease in headache severity in the capsaicin group on days 8–15 compared to days 1–7, but not in the placebo group. Episodic CH patients appeared to benefit more than chronic CH patients. These results indicate that intranasal capsaicin may provide a new therapeutic option for the treatment of this disease.