B.M. Fusco

Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man

1 Topical application of capsaicin to the human nasal mucosa induced a burning sensation and sneezing. A dose‐dependent seromucous nasal secretion was also observed. Capsaicin (75 μg) was more potent than methacholine (50 mg) in producing nasal secretion, while topical histamine (200 μg), substance P (135 μg) and calcitonin gene‐related peptide (36 μg) did not induce rhinorrhea. 2 Pretreatment with either topical ipratropium bromide, systemic dexchlorpheniramine or indomethacin did not influence the effects induced by capsaicin. Topical pretreatment with lidocaine inhibited the painful sensation but failed to block the rhinorrhea. Desensitization to the effects of capsaicin occurred following 4–5 subsequent applications, and full recovery was observed within 30–40 days. 3 It is proposed that the effects of capsaicin in human nasal mucosa are due to excitation of primary afferent neurones that (a) convey burning and painful sensation, (b) evoke a sneezing reflex and (c) induce nasal secretion by releasing transmitter(s) from their peripheral terminals.

Beneficial effect of capsaicin application to the nasal mucosa in cluster headache.

Abstract: Capsaicin application to human nasal mucosa was found to induce painful sensation, sneezing, and nasal secretion. All of these factors exhibit desensitization upon repeated applications. The acute effects induced by capsaicin (300 μg/100 μl) application to the nasal mucosa were studied in healthy volunteers and cluster headache patients. These effects were not different in both nostrils of cluster headache patients as well as in the single nostril of healthy controls. Likewise, the time course of desensitization to the painful sensation and nasal secretion induced by capsaicin applied for five consecutive days in control subjects was almost superimposable to those observed in the nasal mucosa of cluster headache patients. The number of spontaneously occurring attacks was significantly reduced in the 60 days after the end of capsaicin treatment. Whether the beneficial effect induced by capsaicin application to the nasal mucosa could be ascribed to a specific action on sensory neurons remains unknown.

Preventative effect of repeated nasal applications of capsaicin in cluster headache

&NA; Preliminary studies have shown that repeated nasal applications of capsaicin prevented the occurrence of cluster headache attacks. The present study was designed to verify the difference in efficacy of treatment with nasal capsaicin, depending on the side of application. Fifty‐two patients affected by episodic form were divided into 2 groups, one receiving the treatment on the same side where the attacks occurred (ipsilateral side), the other on the controlateral side. Eighteen patients with a chronic form alternately received both ipsilateral and controlateral treatments. Seventy percent of the episodic patients, treated on the ipsilateral side, showed a marked amelioration whereas no improvement was noted in the patients treated on the ontralateral side. The efficcy of ipsilateral treatment was emphasized by the results obtained in chronic patients. However, in these patients, the maximum period of amelioration lasted no more than 40 days. The differnce between the effects of the 2 treatments (contralateral and ipsilateral) was statistically significant in both episodic and chronic sufferers. The efficacy of repeated nasal applications of capsaicin in cluster headache is congruent with previous reports on the therapeutic effect of capsaicin in other pain syndromes (post‐herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia) and supports the use of the drug to produce a selective analgesia.

Analgesic effect of capsaicin in idiopathic trigeminal neuralgia.

Twelve informed and consenting patients were studied to determine the influence of capsaicin, the pungent component of the red pepper, on trigeminal neuralgia. All of these patients had idiopathic trigeminal neuralgia. These patients were followed up for 1 yr after the topical application over the painful area of 1.0 g of capsaicin three times a day for several days. Six patients had complete and four patients had partial relief of pain; the remaining two patients had no relief of pain. Of the 10 patients who were responsive to therapy, four had relapses of pain in 95-149 days. There were no relapses following the second therapy for the remainder of the year. We conclude that the topical application of capsaicin is frequently successful in relieving the pain from trigeminal neuralgia.

Simultaneous release of substance P- and calcitonin gene-related peptide (CGRP)-like immunoreactivity from isolated muscle of the guinea pig urinary bladder

Capsaicin (10 microM) induced a tetrodotoxin (TTX)-resistant release of substance P (SP)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) from muscle strips of the guinea pig isolated urinary bladder. A second application of capsaicin had no effect, indicating a specific effect on sensory nerves (desensitization). In functional experiments, capsaicin produced a phasic contraction of isolated bladder strips. This response was TTX-resistant, exhibited desensitization and was specifically antagonized by [D-Pro4, D-Trp7.9, Phe11] SP(4-11) a SP antagonist which also reduced, at a similar extent, the contraction induced by exogenous SP. These findings provide direct neurochemical and functional evidence for a transmitter role for a SP-like peptide(s) from peripheral sensory terminals in the guinea pig urinary bladder.

Substance P Theory: A Unique Focus on the Painful and Painless Phenomena of Cluster Headache

SYNOPSIS

Idiopathic headache as a possible risk factor for phantom tooth pain

SYNOPSIS

Unilateral impairment of pupillary response to trigeminal nerve stimulation in cluster headache

&NA; The pupillary constriction induced ipsilaterally by transcutaneous electrical nerve stimulation (TENS) of the infratrochlear nerve was measured, using an electronic pupillometer, in 26 episodic cluster headache (CH) and 15 migraine sufferers tested during an attack‐free period and in 16 healthy controls. In controls, TENS gave rise to a miosis which was slow in onset and long‐lasting in duration, and which was comparable to that mediated by tachykinins in animals. A similar miotic response was bilaterally observed in migraine patients and in CH patients examined during the inactive phase. In CH sufferers during the cluster period, TENS only elicited a normal pupillary constriction in the asymptomatic eye, whereas the resulting response in the symptomatic eye was markedly decreased. Although the exact mechanism underlying the dysfunction remains to be clarified, these results seem to indicate that ocular trigeminal pathways are involved in CH.

The pressor hyperresponsiveness to phenylephrine unmasks sympathetic hypofunction in migraine

The pressor responsiveness to phenylephrine, an almost pure agonist of peripheral alpha-1-adrenoceptors, was studied in 32 migraine patients in headache-free intervals. Eighteen healthy volunteers served as a control group. Fourteen patients and 14 controls also underwent the tilt test. The following observations were made: (1) the pressor response to phenylephrine was significantly greater and longer lasting in patients than in controls; (2) the reflex decrease of heart rate did not differ in the two groups; (3) a normal orthostatic increase of blood pressure and heart rate occurred in migraineurs with hyperresponsiveness to phenylephrine. These findings suggest a supersensitivity of vascular adrenoceptors which is compatible with a chronic adrenergic deficiency in migraineurs. Since patients did not show an orthostatic hypotension in attack-free periods, the compensatory character of receptoral supersensitivity and the possible mechanisms of cardiovascular dysautonomia, which may occur during migraineous attack, were discussed.

In vivo pupillary constrictor effects of substance P in man

The ocular effects of substance P (SP) were studied in 13 normal volunteers. Various concentrations of SP (0.135, 1.35 and 135 micrograms per 100 microliters) were instilled into the conjunctival sac and pupillary area changes were evaluated by means of an electronic pupillometer. The ability of SP to modify the mydriasis induced by pretreatment with 1% homatropine eyedrops was also studied. The instillation of SP produced miosis in a dose-dependent manner without provoking any ocular disturbances. Furthermore, the highest concentration tested was unable to reduce the homatropine-induced mydriasis. These findings indicate that SP exerts a pupillokinetic action in humans which probably occurs via a receptor mechanism. Since muscarinic blockade is not overcome by the peptide instillation, the results do not clarify whether SP causes miosis acting on iris muscles and/or cholinergic fibres.