Central pain in multiple sclerosis : clinical characteristics, sensory abnormalities and treatment

Abstract: In the present research programme the occurrence of pain in MS was investigated, with special emphasis on central pain (CP). Questionnaires were sent to all 429 patients with definite MS in the patient register at our neurology department. All admitting to pain were interviewed by telephone and offered an extended interview and examination at the out patient department. 364 patients replied (86%), of whom 58% reported pain during the course of their disease (21% nociceptive, 2% peripheral neuropathic and 1% related to spasticity). 1 DO patients (27,5%) had CP, including 18 patients (4,9%) with trigeminal neuralgia (TN). Non-trigeminal CP was, in 87%, located in the lower extremities and in 31% in the upper. lt was mostly bilateral (76%) and constant, with 88% experiencing daily pain. Only 2% had paroxysmal attacks. Aching, burning and pricking were the commonest qualities. The pain was intense with little 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. Trigeminal neuralgia in our MS patients started later in life and after longer disease duration than did nontrigeminal pain. Both types of CP existed either chronically or as a feature of relapse.Somatosensory abnormalities were analysed in detail using traditional neurological tests and quantitative methods for sensory tests (QST) in 62 patients with non-trigeminal CP and in a control group of 16 patients with MS and sensory symptoms, but without pain. 97 per cent of the CP patients had abnormal sensibility to temperature and pain, compared to 81% in the control group (p<0.05), whereas there was a tendency towards the opposite regarding sensibility to touch, which was decreased in 66% vs. 87% (n.s), vibration (81% vs. 55%; n.s) and to joint movement (32% vs. 62%; p<0.04).Comparison between painful and non-painful regions showed significantly more abnormal sensibility, in the CP regions, for warmth (p<0.001 ), cold (p<0.05), difference limen (innoxious warmth and cold, p<0.01), cold pain (p<0.01), and heat pain/cold pain combined (p<0.001). There were similar differences between CP regions and regions with sensory symptoms, in the controls, for warmth (p<0.05), cold (p<0.01), difference limen (innoxious warmth and cold, p<0.01) and heat pain/cold pain combined (p<0.001).These results indicate that MS patients with CP have lesions affecting the spinothalamo-cortical pathways (temperature and pain), and that the lesions affect the mediallemniscal pathways (touch, position sense and vibration) to a lesser degree. The opposite was found in the control group.The results support the general hypothesis that only patients who have lesions affecting the spinothalamo-cortical pathways run the risk of developing CP.23 MS patients with non-trigeminal CP participated in a double-blind 3-phase, crossover, placebo-controlled study on the pain-relieving effect of amitriptyline and carbamazepine. Each drug was given in randomised order, for a period of 4 weeks, separated by a one-week washout. The target dose was 75 mg for amitriptyline and 600 mg for carbamazepine (reduced from 800 mg because of side-effects). The effect of treatment was assessed by daily ratings of pain using a 10-step verbal rating scale and at the end of each treatment period by a global rating 5-step verbal scale. Due to the high incidence of side-effects 12 and 7 patients discontinued carbamazepine and amitriptyline, respectively. For carbamazepine, these occurred at unexpectedly small doses; 100-200 mg. Amitriptyline, but not carbamazepine, showed a statistically significant pain reduction compared to placebo (p<0.05). According to the global rating, nine of 14 patients were responders. The effect was already noticed during the second week of treatment and it appeared to be correlated to the plasma concentration. Two of 9 patients treated with carbamazepine reported some pain relief, but the effect did not reach statistical significance compared to placebo, and no correlation was found between effect and plasma concentration.14 opioid-free patients with non-trigeminal CP caused by MS were investigated. Placebo (normal saline), morphine and naloxone were given intravenously in a standardised manner. The design was a non-randomised, single blind, placebo-controlled trial. For pain assessment a visual analogue scale (0-100 mm) was used. Four patients were opioid-responders, i.e. experienced minimal or no effect on pain with placebo, >50% pain reduction after morphine, and >25% pain increase when naloxone was given after morphine. However, the response was obtained only after high doses of morphine (mean 41 mg). Thus, in contrast to nociceptive pain, only a minority of the patients with CP due to MS responded to morphine and only at high doses. These results are in accordance with experimental studies indicating that neuropathic pain is poorly responsive, but not totally unresponsive to opioids.