Thermal and tactile sensory deficits and allodynia in a nerve-injured patient: a multimodal psychophysical and functional magnetic resonance imaging study

OBJECTIVE: A case study was conducted to examine a patient with chronic neuropathic pain of the right foot following peripheral nerve injury and characterize associated sensory abnormalities. METHODS: Multimodal psychophysical examination of the patient's affected and nonaffected foot included thermal sensibility, dynamic touch, and directional sensibility. In addition, we used functional magnetic resonance imaging to study cortical representation of brush-evoked allodynia. RESULTS: Detailed psychophysical examination revealed substantial deficits in warm, cool, and tactile perception on the injured foot. These findings indicated severe dysfunction of perceptual processes mediated by A beta, A delta, and C fibers. Despite reduced tactile perception, light touch evoked a deep burning pain in the foot. Functional magnetic resonance imaging during brushing of the patient's injured foot showed that tactile allodynia led to activation of several cortical regions including secondary somatosensory cortex, anterior and posterior insular cortex, and anterior cingulate cortex. Brushing of the patient's nonaffected foot led to fewer activated regions. DISCUSSION: The profound sensory disturbances suggest a possible deafferentation type of tactile allodynia mediated by changes within the central nervous system, such as a disruption of normal tactile or thermal inhibition of nociception. The functional magnetic resonance imaging data suggest that tactile allodynia is represented in similar brain regions as experimental pain.     

Difference in triptan effect in patients with migraine and early allodynia

The aim of this study was to determine whether in migraine patients with and without aura early treatment with various triptans leads to differences in pain reduction after 1 h and in modulating cutaneous allodynia. Thirty-six patients with early manifestation of a clinically recognizable allodynia of the face and non-responders to earlier treatment with sumatriptan 100 mg were included. Patients were randomized to six triptan treatment groups. Significant pain reduction was seen only in the group receiving zolmitriptan nasal spray 5 mg with a mean visual analogue scale (VAS) score of 3.8 (s.d. 1.2) at baseline and 2.4 (s.d. 1.3; P = 0.015) at 1 h after using the triptan and was thus a predictor of a VAS score 3 within 1 h. The study results indicate that migraine headache intensity can be reduced within 1 h by using zolmitriptan 5 mg nasal spray in spite of the presence of early cutaneous allodynia.     

Allodynia in patients with post-stroke central pain (CPSP) studied by statistical quantitative sensory testing within individuals

The disinhibition hypothesis of post-stroke central pain (CPSP) suggests that 'the excessive response (dysesthesia/hyperalgesia/allodynia) is accompanied by a em leader loss of sensation' resulting from a lesion of a 'lateral nucleus' of thalamus or of 'cortico-thalamic paths' [Brain 34 (1911) 102]. One recent elaboration of this hypothesis proposes a submodality specific relationship, such that injury to a cool-signaling lateral thalamic pathway disinhibits a nociceptive medial thalamic pathway, thereby producing both burning, cold, ongoing pain and cold allodynia. The current study quantitatively evaluated the sensory loss and sensory abnormalities to discern submodality relationships between these sensory features of CPSP. The present results were statistically tested within individuals so that sensory loss and sensory abnormality are directly related by occurrence in the same individual. The results demonstrate that individuals with CPSP and normal tactile detection thresholds experience tactile allodynia significantly more often than those with tactile hypoesthesia. Most patients (11/13) exhibited hypoesthesia for the perception of cool stimuli, but few of these (2/11) showed cold allodynia. The most dramatic case of cold allodynia occurred in a patient who had a normal detection threshold for cold. Individuals with cold hypoesthesia, strictly contralateral to the cerebro-vascular accident (CVA or stroke), were often characterized by the presence of burning, cold, ongoing pain, and by the absence, not the presence, of cold allodynia. Overall, these results in CPSP suggest that tactile allodynia occurs in disturbances of thermal/pain pathways that spare the tactile-signaling pathways, and that cold hypoesthesia is neither necessary nor sufficient for cold allodynia.     

On the repeatability of brush-evoked allodynia using a novel semi-quantitative method in patients with peripheral neuropathic pain

Using a semi-quantitative method the repeatability of brush-evoked allodynia was examined within and between days in nine patients with spontaneous ongoing pain and dynamic mechanical allodynia due to peripheral neuropathy. In addition, the relationship between the intensity of spontaneous ongoing pain and the total brush-evoked pain intensity was addressed. The brush stimulus was applied in the innervation territory of the lesioned nervous structure by lightly stroking 60 mm of the skin four times with an 8 mm wide brush. Using a computerized visual analogue scale the patients continuously rated the intensity and duration of brush-evoked allodynia and the total brush-evoked pain intensity was calculated as the area under the curve. The patients were examined 4 days during one month, i.e. at day 1, 3, 28 and 30 and each study day the stimulus was repeated four times with an inter-stimulus interval of 10 min. The variation between repeated assessments was analyzed using the intraclass correlation coefficient and the total brush-evoked pain intensity within days ranged from 0.89 to 0.95 ("very good repeatability") and between days from 0.77 to 0.97 ("very good repeatability"). A significant positive correlation was demonstrated between the mean intensity of spontaneous ongoing pain and the mean total brush-evoked pain intensity (r(s)=0.68, P<0.042, "a moderate to good correlation").     

Differential recruitment of endogenous pain inhibitory systems in neuropathic pain patients

Neuronal hyperexcitability is a key finding in patients with neuropathic pain. Contributing to hyperexcitability may be decreased activity in the endogenous pain inhibitory systems. The present study aimed at recruiting descending inhibition, by the use of painful heterotopic stimulation (HTS), in 16 patients with peripheral chronic neuropathic pain and associated brush-evoked allodynia. Two experiments were performed: one examined the effect of HTS on ongoing pain and intensity of brush-evoked allodynia and the other tested the effect of HTS on ongoing pain and area of brush-evoked allodynia. Both experiments consisted of two sessions, one with painful cold HTS (1 degrees C water bath) another with non-painful neutral HTS (32 degrees C water bath). The area of brush-evoked allodynia was significantly reduced (P=0.003) during painful HTS, as compared to non-painful HTS. In contrast, neither the intensity of brush-evoked allodynia nor the ongoing pain was significantly changed. The results indicate that endogenous pain modulating systems can alter some aspects of chronic neuropathic brush-evoked allodynia. The differential effect of painful HTS on ongoing pain and area of brush-evoked allodynia suggest that separate mechanisms are involved.     

Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan

Sumatriptan and the other triptan drugs target the serotonin receptor subtypes1B, 1D, and 1F (5-HT(1B/D/F)), and are prescribed widely in the treatment of migraine. An anti-migraine action of triptans has been postulated at multiple targets, within the brain and at both the central and peripheral terminals of trigeminal "pain-sensory" fibers. However, as triptan receptors are also located on "pain-sensory" afferents throughout the body, it is surprising that triptans only reduce migraine pain in humans, and experimental cranial pain in animals. Here we tested the hypothesis that sumatriptan can indeed reduce non-cranial, somatic and visceral pain in behavioral models in mice. Because sumatriptan must cross the blood brain barrier to reach somatic afferent terminals in the spinal cord, we compared systemic to direct spinal (intrathecal) sumatriptan. Acute nociceptive thresholds were not altered by sumatriptan pre-treatment, regardless of route. However, in behavioral models of persistent inflammatory pain, we found a profound anti-hyperalgesic action of intrathecal, but not systemic, sumatriptan. By contrast, sumatriptan was completely ineffective in an experimental model of neuropathic pain. The pronounced activity of intrathecal sumatriptan against inflammatory pain in mice raises the possibility that there is a wider spectrum of therapeutic indications for triptans beyond headache.     

Pain thresholds in daily transformed migraine versus episodic migraine headache patients

OBJECTIVE: The objective of this study was to test whether pain thresholds of patients with episodic migraine (EM) are significantly different from transformed migraine (TM) patients as measured by Quantitative Sensory Testing (QST) and Semmes-Weinstein Monofilaments (SW). BACKGROUND: Although there are many theories, none have undeniably proven why many TM patients are refractory to triptans and other gold standard medications. The hypothesis was that baseline pain thresholds of TM patients are lower than EM patients. METHODS: Episodic (n = 40) and Transformed (n = 41) migraineurs with and without aura were examined with QST and SW over eight locations (bilateral ophthalmic, maxillary, C4/posterior neck, and forearm). All patients completed two visits, baseline and severe migraine. RESULTS: TM patients have lower pain thresholds, than EM patients, as measured on QST and SW testing. A total of 81 out of 129 patients completed both parts of the study at baseline and severe migraine. There were significant differences (P < .05) between EM and TM groups at baseline on maxillary, neck (EM = 45.91 degrees C and TM = 42.94 degrees C), and arm. CONCLUSIONS: TM patients, clinically known to report skin hypersensitivity during migraine, were found to have lower pain thresholds than EM patients, both with severe migraine, and at baseline, measured by QST and SW mechanical testing. As with Burstein's work in EM patients with lowered pain thresholds during their acute migraine, central sensitization may be the explanation for non-responsiveness to triptans in a high proportion of TM patients. The difference in pain threshold at the neck location was such a strikingly frequent difference between EM and TM patients, that this indicates the need for future research to clarify the directional relationship and the relative importance of muscular versus peripheral versus central hypersensitivity in the determination of allodynia.     

Sumatriptan 6 mg subcutaneous as an effective migraine treatment in patients with cutaneous allodynia who historically fail to respond to oral triptans

The objective of the study was to assess the efficacy of 6 mg subcutaneous (SC) sumatriptan to treat migraine and the relationship between response of migraine and cutaneous allodynia in a population of migraine patients who historically failed to respond to oral triptan medications. This was an openlabel study consisting of patients with migraines who historically failed to respond to oral triptan medications. Forty-three patients were asked to treat three migraine attacks with 6 mg SC sumatriptan. The primary efficacy endpoint was the percentage of patients achieving relief of headache at 2 h. Ninetyone percent of the patients responded to a single dose of SC sumatriptan 6 mg. Fifty percent of all patients were pain-free by 2 h and over 30% had a 24-h sustained pain-free response. When administered within 90 min from the onset of migraine (i.e., during the developing phase of cutaneous allodynia), SC 6 mg sumatriptan proved to be effective despite the occurrence of allodynia in a group of patients, who historically had failed to respond to oral triptan medications. These findings suggest that the window of opportunity to treat allodynic patients with injectable triptans may be longer (up to 2 h) than with oral triptans (up to 1 h).     

Dynamic and static components of mechanical hyperalgesia in human hairy skin.

The principle finding of the present study is that there are two types of mechanical hyperalgesia developing in human hairy skin following injurious stimuli. Mechanical hyperalgesia comprises a dynamic component (brush-evoked pain, allodynia) signalled by large myelinated afferents and a static component (hyperalgesia to pressure stimuli) signalled by unmyelinated afferents. While the static component is only found in the injured area, the dynamic component also extends into a halo of undamaged tissue surrounding the injury. The irritant chemicals, mustard oil or capsaicin, were applied transdermally in 20 subjects to a patch (2 x 2 cm) of hairy skin. Both substances evoked burning pain and hyperalgesia to mechanical stimuli. While stroking normal skin with a cotton bud was perceived only as touch prior to chemical stimulation, there was a distinctly unpleasant sensation afterwards. This component of mechanical hyperalgesia persisted for at least 30 min and was present in the skin exposed to the irritants (primary hyperalgesia) as well as in a zone of untreated skin surrounding the injury (secondary hyperalgesia) measuring 38 +/- 4 cm2 after capsaicin. Pressure pain thresholds dropped to 55 +/- 8% of baseline level after mustard oil and to 46 +/- 9% after capsaicin. However, this drop of thresholds was short-lived, lasting 5 min following mustard oil but persisting more than 30 min following capsaicin treatment. The reduction of pressure pain thresholds was only observed for treated skin areas, but not in the surrounding undamaged tissue from where brush-evoked pain could be evoked. When pressure pain thresholds were lowered, the pain had a burning quality which differed distinctly from the quality of brush-evoked pain. On-going burning pain and both types of mechanical hyperalgesia were critically temperature dependent. Mildly cooling the skin provided instant relief from on-going pain, abolished brush-evoked pain and normalized pressure pain thresholds. Rewarming resulted in a reappearance of on-going pain and hyperalgesia. The effect of a nerve compression block of the superficial radial nerve on these sensations was tested in 14 experiments. When the ability to perceive light touch had been abolished, there was also no touch-evoked pain, indicating that this component of mechanical hyperalgesia is mediated by large-diameter primary afferents. At a later stage of the block when the subjects' ability to perceive cold stimuli had also been lost, application of cool stimuli still eliminated on-going burning pain, suggesting that pain relief afforded by cooling the skin acts at the peripheral receptor level and not by central masking.(ABSTRACT TRUNCATED AT 400 WORDS)     

Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors

OBJECTIVE: To determine whether delayed infusion of COX1/COX2 inhibitors (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress ongoing sensitization in central trigeminovascular neurons in the rat. BACKGROUND: The majority of migraineurs seeking secondary or tertiary medical care develop cutaneous allodynia during the course of migraine, a sensory abnormality mediated by sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain free within a narrow window of time (20 to 120 minutes) that opens with the onset of pain and closes with the establishment of central sensitization. Can drugs that tackle ongoing central sensitization render allodynic migraineurs pain free after the window for triptan therapy has expired? METHODS: Patients exhibiting migraine with allodynia were divided in two groups (n=14, each): group 1 received delayed sumatriptan injection (6 mg) 4 hours after onset of attack--which failed to render them pain free-and ketorolac infusion (two 15-mg boluses) 2 hours later; group 2 received delayed ketorolac monotherapy 4 hours after onset of attack. Pain intensity (visual analog scale) and skin sensitivity (quantitative sensory testing) were measured when the patients were migraine free (baseline); 4 hours after onset of migraine (just before treatment); 2 hours after sumatriptan; 1 hour after ketorolac. In the rat, we tested whether infusion of ketorolac (0.4 mg/kg) or indomethacin (1 mg/kg) will block ongoing sensitization in peripheral and central trigeminovascular neurons. The induction of sensitization (using topical application of inflammatory soup on the dura) and its suppression by COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity and responses to mechanical and thermal stimuli. RESULTS: Patients had normal skin sensitivity in the absence of migraine, and presented cutaneous allodynia 4 hours after onset of migraine. In group 1, all patients continued to exhibit allodynia 2 hours after sumatriptan treatment, and none of them became pain free. However, 71% and 64% of the patients in groups 1 and 2, respectively, were rendered free of pain and allodynia within 60 minutes of ketorolac infusion. Nonresponders from both groups, in contrast to the responders, had had a history of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked sensitization in meningeal nociceptors and suppressed ongoing sensitization in spinal trigeminovascular neurons. This inhibitory action was reflected by normalization of neuronal firing rate and attenuation of neuronal responsiveness to mechanical stimulation of the dura, as well as mechanical and thermal stimulation of the skin. CONCLUSIONS: The termination of migraine with ongoing allodynia using COX1/COX2 inhibitors is achieved through the suppression of central sensitization. Although parenteral administration of COX1/COX2 inhibitors is impractical as routine migraine therapy, it should be the rescue therapy of choice for patients seeking emergency care for migraine. These patients should never be treated with opioids, particularly if they had no prior opioid exposure.     

Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan

The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double-blind cross-over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6) was less pleasant (p<0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n=6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low-threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.     

Quantitative sensory testing before and after regional guanethidine block in patients with neuralgia in the hand.

Using reference values from healthy volunteers, thermal and vibration-induced pain thresholds and the sensibility for warm and cold were studied in 18 patients with neuralgia in one hand following a traumatic injury or surgery. All patients had spontaneous pain and allodynia to vibration. They were treated with intravenous regional guanethidine block (RGB). Quantitative sensory testing was performed on both hands before and 1-3 days after treatment. Eleven patients benefitted considerably from the block, with pain relief for 2 weeks or more. Ten of these 11 patients had mild nerve injuries caused by compressive trauma to the nerve. Before RGB they showed a moderate loss in temperature discrimination capacity; their heat pain thresholds were reduced and they exhibited allodynia to cold and vibration on the injured side. After RGB, the pain thresholds were normalised both to thermal and vibratory stimuli. These patients were classified as having sympathetically maintained pain (SMP). Seven patients reported no or only minor pain-relieving effect of RGB lasting 1-5 days. Severe nerve injuries were most frequent in this group of patients. On the injured side, before RGB, their ability to discriminate between warm and cold was markedly impaired, thermal pain thresholds were normal, and they showed allodynia to vibration. After RGB, there was no change in thermal pain thresholds and the allodynia to vibration persisted. These patients were classified as having sympathetically independent pain (SIP). The results indicate that quantitative thermal sensory tests, together with clinical evaluation of the nerve trauma, can help to predict which patients will have long-lasting pain alleviation after RGB treatment.     

Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.     

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.     

Clarification of developing and established clinical allodynia and pain-free outcomes

OBJECTIVE: The aim of this study was to determine whether clinical indicators of cutaneous allodynia predict the success of migraine therapy with sumatriptan using a brief questionnaire. BACKGROUND: Using quantitative sensory testing (QST) recent studies demonstrate that the presence of cutaneous allodynia, a clinical manifestation of central sensitization, can be detrimental to the success of migraine therapy with sumatriptan. QST is costly and requires much time, therefore it is not feasible to use in clinical practice. METHODS: In this prospective study, migraineurs completed a questionnaire about their skin sensitivity during migraine. Each migraineur treated 2 migraine headaches with sumatriptan (100 mg): 1 headache at the earliest sign of migraine pain (mild, within 1 hour of onset) and 1 headache at least 4 hours after the onset of pain while moderate or severe. RESULTS: Thirty-six migraine headaches were evaluated in 18 migraineurs. A total of 44% of the headaches were not associated with allodynia at any time. Irrespective of allodynic status, headaches were more likely to become pain-free with early versus late treatment (2 hours; 78% vs. 33%, respectively). Headaches were equally likely to become pain-free when allodynia was reported before treatment but not 2 and 4 hours after treatment (2 hours; 67 vs. 63%, respectively, 4 hours 80 vs. 81%, respectively). However, no headaches were pain-free when allodynia was reported at 2 and 4 hours after treatment. CONCLUSIONS: Headaches without allodynia were aborted when treated early or late, and headaches with allodynia were aborted only when allodynia was not present after treatment. These findings suggest that different mechanisms account for allodynia before and after treatment; a developing phase in which central sensitization depends on incoming pain signals from the peripheral nociceptors and an established phase in which the sensitization becomes independent of the pain signals that come from the dura.     

Referred cutaneous allodynia in a migraine patient without simultaneous headache

Cutaneous allodynia has been described in migraine. We report on a 39-year-old woman with migraine with aura who had cutaneous allodynia to both dynamic (brush) and static (pressure) mechanical stimulation between attacks. For both sensory modalities, the evoked pain on allodynia testing was located to the right frontal area (the location of her usual migraine headache), contralaterally to the stimulated skin area. There was no allodynia when the right frontal area was stimulated directly. We suggest the term 'referred allodynia' for this phenomenon and discuss possible mechanisms for its occurrence.     

Heterotopic noxious conditioning stimulation (HNCS) reduced the intensity of spontaneous pain, but not of allodynia in painful peripheral neuropathy.

In 15 patients with painful peripheral neuropathy and dynamic mechanical allodynia, the influence of spontaneous ongoing neuropathic pain on pain sensitivity in a remote pain-free area was examined, as was the influence of ischemia-induced heterotopic noxious conditioning stimulation (HNCS) on the intensity of ongoing pain and brush-evoked allodynia. In addition, the modulating effect of HNCS on pain sensitivity in a pain-free area was investigated. Pain thresholds to pressure and heat as well as the sensitivity to suprathreshold pressure- and heat pain were assessed in the pain-free area. Dynamic mechanical allodynia was induced by a recently developed semi-quantitative brushing technique and the patients continuously rated the intensity of the allodynia using a computerized visual analogue scale (VAS). The total brush-evoked pain intensity was calculated as the area under the VAS curve. At baseline, no significant difference in pain sensitivity was found between patients and their healthy controls in the pain-free area, indicating a lack of activation of pain modulatory systems from the spontaneous pain. Compared to baseline, the patients rated the ongoing neuropathic pain intensity significantly lower during the HNCS-procedure (p<0.05). In contrast, there was no influence from HNCS on the total brush-evoked pain intensity. In the pain-free area higher pressure pain thresholds were demonstrated during conditioning stimulation in patients and controls alike (p<0.01). In controls only, a significantly higher heat pain threshold was found during the HNCS-procedure (p<0.01). The main finding of the present study was that HNCS altered differentially spontaneous and brush-provoked pain in patients with painful peripheral neuropathy.     

Acute pharmacotherapy of migraine,tension-type headache,and cluster headache

Abstract In most migraine patients acute therapy is needed. Migraine can be treated either with specific drugs, the triptans and ergot alkaloids, or with NSAIDs. Triptans are a major step foreward in migraine therapy. The therapeutic gain for headache relief is 50% for subcutaneous sumatriptan whereas it is 30-40% for most oral triptans. After oral triptans sustained pain free is only 30%. There is thus still ample room for improvement of acute therapy in migraine. For tension-type headache there is no specific therapy and it is treated with NSAIDs. Only 17-32% become pain free after these drugs. For attacks of cluster headache oxygen and subcutaneous sumatriptan can be used. Intranasal triptans can be an alternative.