Pain is more common in multiple sclerosis (MS) than has previously been recognised. In the present study we have investigated the occurrence of central pain (CP) in MS and defined its characteristics. Questionnaires were sent to all 429 patients with definite MS in the patient register at our neurology department. All admitting to pain were interviewed and offered an extended interview and examination. Three hundred and sixty four patients responded (86%), of whom 57.5% reported pain during the course of their disease (21% nociceptive, 2% peripheral neuropathic and 1% related to spasticity). One hundred patients (27.5%) had CP, including 18 patients (4.9%) with trigeminal neuralgia. The non-trigeminal CP was, in 87%, located in the lower and in 31% in the upper extremities. It was mostly bilateral (76%) and constant, with 88% experiencing daily pain. Only 2% had paroxysmal attacks. Aching, burning, pricking were the commonest qualities. The pain was intense with small to moderate spontaneous variation. In 5.5% of all patients (20% of the patients with CP), pain was a presenting symptom, alone or in combination with other symptoms. The most common neurological symptoms/signs besides CP were sensory abnormalities (98%, dominated by abnormal sensibility to painful stimulus and temperature). Trigeminal neuralgia in MS started later in life and after longer disease duration than non-trigeminal pain. Both types of CP existed either chronically or as a feature of relapse. Central pain is thus an important symptom in MS (around 30%) and causes much suffering.

The intention of the present study was to characterize patients with central post-stroke pain (CPSP) with regard to type and location of the cerebrovascular lesion (CVL), the characteristics of the pain and the neurological symptoms and signs in addition to the pain. Twenty men and 7 women with a mean age of 67 years and a mean pain duration of 44 months were examined 9-188 (mean 53) months after their stroke. The clinical symptoms and signs and the CT scans indicated that the CVL were located in the lower brain-stem in 8 patients, involved the thalamus in 9 patients and were located lateral and superior to the thalamus in 6 patients. In the remaining 4 patients the location of the CVL could not be determined with certainty. The 3 identified hematomata were all located in the thalamus. The onset of the pain was immediate in 4 patients, within the first post-stroke months in 10 patients and delayed by 1-34 months in the rest. The pain was on the left side in 18 patients. Twenty patients had hemipain. Most patients experienced more than one type of pain. The most common qualities were burning, aching, pricking and lacerating, with some differences in the frequencies according to the location of the CVL. Burning pain was most common, except among the patients with thalamic CVL, in whom lacerating pain was more common. Aching and pricking pain were also frequent. All patients considered the pain to be a great burden and most rated the pain intensity as high on a visual analogue scale. The intensity was increased by external stimuli, the most common being joint movements, cold and light touch. Five patients reported aggravation by emotional stimuli. Besides pain, the only neurological symptom common to all patients was decreased temperature sensibility, as shown by quantitative methods. It is possible that pain sensibility was also abnormal in all. Hypersensitivities to cutaneous stimuli, including evoked dysesthesias were found in 88% of the patients, while the detection thresholds for touch and vibration were abnormal in only 52% and 41%, respectively. Similarly, low figures were found for paresis and ataxia, which were present in 48% and 62%, respectively. It is concluded that only a minority of patients with central pain after stroke have thalamic lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

The somatosensory abnormalities in 20 men and 7 women (mean age 67 years, range 53-81) with central post-stroke pain (CPSP) have been analysed in detail with traditional neurological tests and quantitative methods. The cerebrovascular lesions were located in the lower brain-stem in 8 patients, involved the thalamus in 9 and in 6 were suprathalamic. In 4 patients the location of the CVL could not be determined. All patients had abnormal temperature and pain sensibility, with a severe deficit in most cases. All except 2 had raised thresholds to thermal pain and all except 1 had abnormal sensibility to pin-prick. Eighty-eight percent exhibited hyperpathia with combined loss and suprathreshold exaggeration of somatic sensibility. In 85% somatic stimuli evoked dysaesthesia and about half of these patients also experienced spontaneous dysaesthesia. Paraesthesias were reported by 41%, radiation of stimuli by 50%, after-sensations by 45% and allodynia by 23%. Vibration sensibility was abnormal in 41%; raised thresholds to the perception of touch were found in 52%, to 2-PD in 35%, to dermolexia in 45% and to joint movements in 37%. The results indicate that all patients with CPSP have lesions that affect the major pathways for temperature and pain sensibility, i.e., the spino-thalamo-cortical pathways. Furthermore it appears that neither the level of the lesion along the neuraxis nor concomitant injury to the medial lemniscal pathways is crucial for the development of CPSP. The results confirm the notion that CPSP is a deafferentation syndrome, but they also provide evidence against the hypothesis that CPSP is a release phenomenon caused by a lesion that removes inhibitory influences of the lemniscal pathways on neurones that evoke pain.

A double-blind, 3-phase, cross-over, placebo-controlled trial of the pain-relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post-stroke pain (CPSP) but without signs of depression. Treatment was given, in randomized order, for periods of 4 weeks, separated by 1 week wash-out. The final doses were 75 and 800 mg/day, respectively, for amitriptyline and carbamazepine. The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale. For the assessment of depression the Comprehensive Psychopathological Rating Scale (CPRS) was used. Amitriptyline produced a statistically significant reduction of pain when compared to placebo. According to the global rating, 10 of the 15 patients were responders to this drug. The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration, since the median total ami- and nortriptyline concentrations were 497 and 247 nmol/l, respectively, for responders and non-responders. The early onset, together with the fact that the patients were not depressed, nor did they obtain reduced scores on ratings of depressive symptoms and signs, provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect. Five of the 14 patients treated with carbamazepine reported some pain relief, but the effect did not reach statistical significance when compared to placebo. No correlation was found between effect and plasma concentration. In general, the patients tolerated the planned final dose of amitriptyline well. No final dose reduction was necessary. Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients. However, only 1 patient had to be taken off medication, on day 25, due to drug interaction.

Sudden onset headache is a common condition that sometimes indicates a life-threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache=TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants >18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.

A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks' washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p=0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p=0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p=0.0016). Both the Patient (p=0.023) and Clinician (p=0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness.

No abstract

The projections of the spinothalamic tract in the macaque monkey have been reinvestigated using the Wiitanen modification of the Fink-Heimer technique. In agreement with previous studies in the monkey (mehler, Bowsher, Kerr) it was found that the spinothalamic tract ascends outside the medial lemniscus, enters the thalamus just dorsal to this structure, and terminates in the posterior, intralaminar and ventral regions, as well as in the zona incerta. The posteromedial nucleus (POm) receives a dense spinothalamic projection medially and ventromedially; elsewhere in the POm the projection is more scattered. The fibers to the intralaminar region terminate in the nucleus centralis lateralis (CL) with a distinct pattern of the distribution. The nucleus centralis medialis (CeM) has a minute projection. There was no evidence for somatotopic organization in the projections to the POm or to the intralaminar region. The distribution of the terminal degeneration in the ventral region was more complex. Although present in the whole nucleus ventralis posterolateralis (VPL), the degeneration was unevenly distributed and also extended beyond the VPL. So-called clusters of dense degeneration lay in the outskirts of the forelimb and hindlimb representation areas, namely at its ventral, ventrolateral, dorsolateral, and medial borders. Centrally the degeneration was scattered. Thus, most of the VPL receives only a sparse spinothalamic projection, but a small portion contains dense networks of terminal spinal fibers. A somatotopic pattern was evident, for after low thoracic lesions most of the medial VPL lacked degeneration. Spinothalamic fibers pass beyond the VPL to terminate in a zone of transition (nucleus ventralis intermedius of V.im of Hassler, '59; Mehler, '71) between the rostral pole of the VPL and the nucleus ventralis lateralis (VL). This zone also reportedly receives cerebellar and vestibular afferent fibers. Observations suggesting that the evolution of the spinothalamic tract and the spino-cervico-thalamic pathway in carnivores and primates may be linked are discussed. The spinothalamic clusters in the monkey's VPL appear to be homologous to much of the cervicothalamic tract projection to the VPL in the cat.