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.

The central and peripheral nervous systems are variably affected in the rheumatic diseases. Automated standardized infrared pupillometry allows the safe, noninvasive assessment of the pupillary innervation. Pupillometry has already been used in studying the autonomic nervous system (ANS) in various rheumatic diseases. In systemic lupus erythematosus, the irideal parasympathetic branch of ANS was more affected then the sympathetic branch. In Sjögren's syndrome, signs of pupillary parasympathetic denervation have been reported. In rheumatoid arthritis, pupil parasympathetic dysfunction has been shown to correlate with ocular dryness. In systemic sclerosis (SSc), both sympathetic and parasympathetic irideal impairment have been demonstrated. Beside providing autonomic innervation, sensory nerves fibers are able to control iris diameter. Exogenous ocular instillation of substance P (SP), a sensory neuropeptide, can determine an omathropine-resistant, non-cholinergic myosis, acting on specific receptors present on the iris sphincter muscle. We first studied pupillary SP-ergic responsiveness in SSc, evaluating substance P (SP)-stimulated pupillary diameters by pupillometry. A higher basal and SP-stimulated myosis was found in lSSc versus both dSSc and controls, whereas no differences existed between dSSc and controls. From the literature, the pupillary parasympathetic nervous system seems to be more affected than the sympathetic branch of ANS in the rheumatic diseases characterized by an inflammatory status. However, we found in SSc both sympathetic and parasympathetic pupil control to be equally impaired. From our experience, we conclude that pupillary nervous control is differently affected in the two subsets of SSc, and that the SP-ergic system seems to be impaired only in lSSc.

Hypertension could be one of the factors leading to exacerbation of the frequency and severity of attacks, both in migraine and tension-type headache. Hypertension has important therapeutic implications and should be actively sought in headache patients, and more thoroughly investigated, with ad-hoc surveys in the general population.

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A short-lasting over-distension of the hand-forearm veins, obtained through a non-invasive original maneuver (Hand Arm Vein Distension test) induces local pain when applied to migraine sufferers in inter-critical period. Conversely, subjects with an absolutely negative personal and family history for any type of idiopathic headache do not report any pain or only an uncertain, slight one. The injection of 1 mL of 2% to 8% (i.e. 0.34 mol/L to 1.36 mol/L) hypertonic saline into the antecubital vein during an extemporary short (1 minute) circulatory blockage (ischemia induced to guarantee a strictly local action of the chemical stimulus) provokes moderate, strong or unbearable local (arm vein) pain in migraine sufferers but not in subjects with a personal and family history absolutely free from any type of headache. These results show for the first time that migraineurs show a proneness to visceral pain in viscera (veins) distant from the head (arm-hand). Such a finding is consistent with the theory that migraine pain is due to a central derangement of the viscerosensory system.