Armando Perrotta

Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control

Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache (MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine (EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings.

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brains electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes.

Facilitated temporal summation of pain at spinal level in Parkinson's disease

Pain is one of the major nonmotor symptoms of Parkinsons disease. We hypothesized that Parkinsons disease patients could show an early diffuse abnormal processing of the nociceptive inputs also in the absence of clinical pain syndrome and that this could represent the physiopathological substrate to explain the high incidence of diffuse pain symptoms.

Trigemino-cervical-spinal reflexes in humans

INTRODUCTION Electrical stimulation of the supraorbital nerve (SON) induces late reflex responses in the neck muscles; these responses are hypothesised to be polysynaptic reflexes participating in a defensive withdrawal retraction of the head from facial nociceptive stimuli. Such responses may extend to the proximal muscle of the arms. OBJECTIVE (1) to investigate reflexes in the upper limb muscles (trigemino-spinal responses, TSR) and their relationship with trigemino-cervical responses (TCR); and (2) to identify the nociceptive component of such reflexes and their functional significance. METHODS Reflex responses were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the SON in 12 healthy subjects. The sensory (ST), painful (PT) and reflex thresholds, the latency and area of the responses, the effect of heterotopic painful stimulation (HTP), the recovery cycle as well as the effect of the expected and unexpected stimuli were measured. RESULTS Stable reproducible TCR and TSR responses were identified at 2.5+/-0.4 x ST, which corresponded exactly to the PT in all the subjects. The TCR and TSR areas were markedly reduced after HTP. The recovery cycle of the TSR area was faster than that of the TCR. Repeated rhythmic stimulation failed to induce progressive reflex suppression. CONCLUSIONS These results confirm the nociceptive nature of the TCR and indicate that the biceps brachii response (TSR) has the same nocifensive significance as the posterior neck muscle responses. TCR and TSR are mediated different polysynaptic pathways The presence of trigemino-cervical-spinal responses in our study clearly indicates that there is a reflex interaction between nociceptive trigeminal afferents and both upper and lower cervical spinal cord motoneurons.

The wolframin His611Arg polymorphism influences medication overuse headache

Homozygosis for wolframin (WFS1) mutations determines Wolfram syndrome (WS), and common polymorphisms of WFS1 are associated with psychiatric illnesses and dependence behaviour. To test the influence of WFS1 polymorphisms on medication overuse headache (MOH), a chronic headache condition related to symptomatic drugs overuse, we analyzed 82 MOH patients for the WFS1 His611Arg polymorphism, and performed a comparison between clinical features of Arg/Arg (R/R) and non-R/R individuals. Individuals harbouring the R/R genotype showed significantly higher monthly drug consumption (t=-3.504; p=0.00075) and more severe depressive symptoms on the BDI questionnaire (t=-3.048; p=0.003) than non-R/R. WFS1 polymorphism emerged as the only significant predictor of drug consumption, at the multivariate regression analysis (F=12.277; d.f.=1,80; p=0.00075, adjusted R2=0.122). These results implicate WFS1 in the clinical picture of MOH, may be through an influence on need for drugs as in other conditions of abuse behaviour.

Four‐week trunk‐specific rehabilitation treatment improves lateral trunk flexion in Parkinson's disease

People with Parkinsons disease (PD) often have a posture characterized by lateral trunk flexion poorly responsive to antiparkinsonian drugs. To examine the effects of a rehabilitation programme (daily individual 90‐minute‐sessions, 5‐days‐a‐week for 4‐consecutive weeks) on lateral trunk flexion and mobility, 22 PD patients with mild to severe lateral trunk flexion, and 22 PD patients without trunk flexion were studied. Patients were evaluated using the Unified Parkinsons Disease Rating Scale motor subscale (UPDRS‐III) score, and the kinematic behavior of the trunk was recorded by means of an optoelectronic system to determine: a) trunk flexion, inclination and rotation values in the erect standing posture; b) ranges of trunk flexion and inclination during trunk movements. After the treatment, significant decreases in trunk flexion [24°(4) vs. 14°(3), P < 0.001] and inclination in the static condition [23°(5) vs. 12°(4), P < 0.001)] were observed, both of which were maintained at the 6‐month follow up. During the trunk flexion task, a significantly increased range of trunk flexion [64°(15) vs. 83°(15), P < 0.001] was observed; similarly, during the lateral bending task, the range of trunk inclination was found to be significantly increased, both toward the side of the trunk deviation [29°(8) vs. 42°(13), P < 0.01] and toward the contralateral side [14°(6) vs 29°(11), P < 0.01]. No further significant changes were observed at the 6‐month follow‐up. Trunk flexion and inclination values in the upright standing posture correlated slightly with the UPDRS‐III score. Our findings show that significant improvements in axial posture and trunk mobility can be obtained through the 4‐week rehabilitation programme described, with a parallel improvement in clinical status.

Reduced habituation of trigeminal reflexes in patients with episodic cluster headache during cluster period

A growing body of evidence supports the pivotal role of the hypothalamus in the pathophysiology of cluster headache (CH). On the basis of animal studies, it has been suggested that a hypothalamic dysfunction can lead to a habituation deficit of brainstem reflex responses, as result of a stress-like condition. Taking into account these findings, we tested the hypothesis that habituation of brainstem reflexes may be impaired in CH patients. The habituation phenomenon of the late components (R2 and R3) of the blink reflex was studied in 27 CH patients during the cluster period, in 22 migraine patients interictally and in 20 control subjects. A significant habituation deficit in the R2 and R3 components was found in CH compared with both controls and migraineurs. The lack of habituation in CH, more pronounced than in migraine, points to abnormal processing of sensory stimuli at the trigeminal level that could be driven by hypothalamic dysfunction during the cluster period.

Facilitated temporal processing of pain and defective supraspinal control of pain in cluster headache

&NA; In cluster headache during the active phase, a facilitation in temporal processing of pain takes place that is related to a defective state‐dependent functional activity of the supraspinal control of pain. &NA; In cluster headache (CH), pathogenesis has been emphasized the role of the posterior hypothalamus. It is part of a supraspinal network involved in the descending control of pain, including the diffuse noxious inhibitory control (DNIC), which in turn modulates the pain processing. We hypothesized that CH during the active phase facilitated temporal pain processing supported by abnormal functioning of the DNIC. We studied the functional activity of the DNIC by evaluating the effect of the cold pressor test (CPT) on the temporal summation threshold (TST) of the nociceptive withdrawal reflex. Ten subjects with episodic CH (2 women, 8 men) and 10 healthy subjects were recruited. Each subject underwent neurophysiological evaluation (nociceptive withdrawal reflex TST and related painful sensation) at baseline, then before (control session), during (pain session), and 5 min after (aftereffect) the CPT (immersing hand in a 4 °C water bath for 4–5 min). Patients had been studied during both the active and remission phases. During the active phase, CH revealed a significant facilitation in temporal processing of pain stimuli (reduction of TST), which reverted during the remission phase. The CPT activating the DNIC did not produce any significant inhibitory effect of pain responses in CH during the active phase, whereas it induced a clear inhibition during the remission phase. We hypothesized that in CH, a dysfunction of the supraspinal control of pain related to the clinical activity of the disease, possibly supported by an abnormal hypothalamic function, leads to a facilitation in pain processing and a predisposition to pain attacks.

Acute reduction of anandamide-hydrolase (FAAH) activity is coupled with a reduction of nociceptive pathways facilitation in medication-overuse headache subjects after withdrawal treatment.

Objectives.— We investigated (1) a possible relationship between the functional activity of the endocannabinoid system and the facilitation of pain processing in migraineurs with medication‐overuse headache, and (2) the effect of withdrawal treatment on both.

Effect of painful heterotopic stimulation on the cutaneous silent period in the upper limbs

OBJECTIVE To evaluate the effect of heterotopic painful stimulation (HPS) on the cutaneous silent period (CSP) and the withdrawal flexor reflex (WFR) in the upper limbs, in an attempt to better identify the nociceptive component of the CSP and its functional relationship with the flexor reflex. METHODS The CSP at different stimulus intensities, the WFR and the H/M ratio were studied in 12 healthy adults. Neurophysiological measurements were recorded in the following 4 conditions: (1) control session; (2) non-painful session (dipping hand in water at 25 degrees C); (3) painful (cold pressor test, CPT); and (4) after-effect (3-8 min after taking hand out of water at 5-6 degrees C). RESULTS During the CPT, the duration of the high-threshold CSP was approximately 23% shorter than the baseline value, the high-threshold CSP latency was approximately 10% longer than the baseline value, and the mean RIII reflex area was approximately 40% smaller than the baseline reflex area (all P<0.05). A significant correlation was found between the percentage decrease in the CSP duration and the WFR area (r=0.61, P<0.05). CONCLUSIONS Our findings indicate that the HPS specifically inhibits both the high-threshold CSP and the WFR, thereby providing further evidence that these cutaneous reflexes are functionally and anatomically related, and that they represent different aspects of a complex nocifensive response.