Federigo Sicuteri

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.

Pain relief by somatostatin in attacks of cluster headache

Abstract The pain relieving effect of somatostatin treatment during 72 attacks of cluster headache in 8 male patients was compared to treatment with ergotamine or placebo in a double‐blind study. Infusion of somatostatin (25 &mgr;g/min for 20 min i.v.) reduced the maximal pain intensity and the duration of pain significantly compared to placebo treatment, and to a degree comparable to ergotamine tartrate treatment (250 &mgr;g i.m.). The results obtained provide new information concerning the possible mechanism of cluster headache attacks and suggest a new therapeutic approach.

Unmasking Latent Dysnociception in Healthy Subjects

SYNOPSIS

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.

SEROTONIN--BRADYKININ POTENTIATION ON THE PAIN RECEPTORS IN MAN.

Abstract Bradykinin produces no pain if injected in small doses into a vein of the back of the hand, but becomes strongly algogenic if serotonin has been previously infused into the vein. The 5-HT pretreated vein is a suitable substrate to the test pain-producing properties of bradykinin and kallidin. By using this substrate, an inverted relationship is noted between the latent period preceding the onset of pain and the dose of bradykinin.

MIGRAINE, A CENTRAL BIOCHEMICAL DYSNOCICEPTION†

PAIN PERCEPTION is a biologic function mediated by the nociceptive system through a multi-integrated, complexly organized nervous mechanism. The activation of this system starts from an adequate stimulus of peripheral pain receptors which then results in perception of pain. The nociceptive system is an alarm system which signals endogenous or exogenous noxious agents affecting the body by means of unpleasant sensations. Pain is particularly useful in the early years of life in teaching the child to avoid noxious agents in the environment. When pain perception is congenitally absent multiple injuries result.

Latent dysautonomic pupillary lateralization in cluster headache. A pupillometric study

Forty-five patients with cluster headache in the asymptomatic phase were studied by electronic pupillography, testing autonomic function of both pupils pharmacologically. Topical sympathetically-acting mydriatics, tyramine and cocaine and the cholinoceptor blocker, homatropine, induced defective mydriatic responses on the symptomatic side, indicating latent impairment of sympathetic function. The abnormality was found in interattack intervals of the cluster period or during intercluster phases. The tyramine test can be proposed for objective diagnosis of cluster headache. We postulate that cluster attacks are triggered and lateralized by a permanent latent unilateral sympathetic dysfunction. Lithium reduced the mydriatic response to tyramine of the pupil contralateral to the pain, thus restoring the equilibrium between both pupils; this therapy may correct the asymmetric sympathetic function by attenuating the activity in the asymptomatic side.

Lowered circannual urinary melatonin concentrations in episodic cluster headache

The circannual secretion of melatonin in 14 Swedish and 15 Italian patients suffering from episodic cluster headache was compared with 14 Swedish and 15 Italian healthy controls matched for sex and age. Overnight samples of urine were collected once a month from 8 to 14 months and kept at -20° C until analysed with RIA. The melatonin concentrations in nocturnal urine were permanently low in cluster headache and there was no consistent change of the melatonin concentration in relation to cluster periods occurring during the study. There was no definitive circannual or infraannual rhythmicity of melatonin in patients or controls. Multiple analysis of variance with repeated measurements showed a significant effect of disease (p < 0.05), but not of time. Sex, geographical location, age, and smoking also had significant effects (p < 0.001) on the melatonin concentrations. Lower melatonin levels in cluster headache patients than in controls may in part be related to a larger number of smokers in the patient group. The relation between tobacco use and melatonin should be further studied.

Release of sensory neuropeptides from dural venous sinuses of guinea pig.

Substance P- and calcitonin gene-related peptide-like immunoreactivities (SP-LI and CGRP-LI, respectively) were measured in superfusates of either superior sagittal sinus and transverse sinuses and attached dura mater or dura mater alone of guinea pig. Exposure of cerebral venous sinuses to capsaicin (1 microM) evoked the release of both SP-LI and CGRP-LI, which was no longer observed upon second challenge with the drug. Neuropeptide release was induced by 80 mM K+ either at the first or second administration. Bradykinin (10 microM) increased the outflow of CGRP-LI, but not of SP-LI, from cerebral venous sinuses. In vitro capsaicin pretreatment (10 microM) or incubation with 10 microM indomethacin completely abolished the bradykinin-evoked CGRP-LI release. Capsaicin (1 microM) failed to evoke release from dura mater without major intracranial venous vessels. Sensory neuropeptide released from the cerebral venous sinuses may take part in certain symptoms, such as vasodilatation and inflammation accompanying the pain of the migraine attack. Bradykinin, putatively via prostanoid generation, may participate in this event.

Dopamine, the second putative protagonist in headache.

PAIN PERCEPTION,1,2 vomiting,3 arterial blood pressure,4-6 and affect,7 funtions involved in migraine and other idiopathic headache (IH), are partially controlled by dopaminergic systems, therefore dopamine8 (DA) and 5-hydroxytryptamine (5-HT)9,10 may have a role in the pathogenesis of IH. It has been suggested that pain in IH is central in nature and caused by impaired processing of painful stimuli in the central nervous system.11 Impaired pain perception or dysnociception, could be the result of brain deficiency of 5-HT,12-14 the main mediator in the antinociceptive system.15-16 We have therefore, investigated drugs which affect turnover, release and the postsynaptic receptors of DA in IH.