Experimental muscle pain provokes long-lasting alterations of thermal sensitivity in the referred pain area.

This study explores thermal sensitivity and thermal nociception for signs of central sensitization in the area of referred muscle pain. Two groups of 24 healthy subjects (ss) each, and with mean ages of, respectively, 27 and 55 years, were first trained in quantitative sensory testing and pain rating. Then, in a second session, referred pain was evoked by injection of 6% hypertonic saline into the infraspinatus muscle. Cold and warm thresholds, synthetic heat threshold (SHT--evoked by an alternating pattern of adjacent cold and warmth), and thermal pain thresholds were measured within the referred pain area at a rate of 1/20 min for 60-120 min. All ss of both groups experienced referred pain mostly in the upper arm and of medium intensity. Pain lasted for approximately 12min with a shorter duration in the older group (p<0.02). The cold threshold increased significantly (p<0.001), and the warm threshold slightly, after the injection and remained high for the whole observation period (i.e. lower and higher temperatures were necessary to elicit cold and warmth, respectively). Threshold recovery was more delayed in the older age group. Of those 28 ss in whom cold pain threshold could be followed during the whole observation period, 18 ss showed an immediate threshold decrease of average 6 degrees C which outlasted the observation period. Four ss responded with a threshold increase. Heat pain thresholds were not affected in the referred pain area. Average synthetic heat threshold did not change; there were, however, distinct and lasting individual threshold shifts in either direction. Ss with lowered cold pain thresholds or evident threshold shifts for synthetic heat had also higher pain ratings. The results demonstrate that experimental muscle pain can induce long-lasting changes in thermal sensitivity and nociception. The unexpected cold threshold increase may tentatively be explained as an expression of long-term depression. The decrease of cold pain threshold or SHT in subgroups of ss may indicate central sensitization. However, the observed changes in this experiment do not provide an unambiguous indicator for central sensitization which seems to be rather individual and might depend on pain intensity and proneness to express central mechanisms of sensitization. Therefore in clinical pain states the individual pattern of sensory abnormalities has to be analysed and interpreted in addition to the pain parameters to assess central involvement.

Delayed recovery of nerve conduction and vibratory sensibility after ischaemic block in patients with diabetes mellitus.

OBJECTIVES: To determine if the recovery of nerve function after ischaemic block is impaired in patients with diabetes mellitus relative to healthy controls. METHODS: Median nerve impulse conduction and vibratory thresholds in the same innervation territory were studied in patients with diabetes mellitus (n = 16) and age matched controls (n = 10) during and after 30 minutes of cuffing of the forearm. RESULTS: Cuffing caused a 50% reduction of the compound nerve action potential (CNAP) after 21.9 (SEM 1.6) minutes in patients with diabetes mellitus and after 10.6 (0.7) minutes in controls. After release of the cuff the half life for CNAP recovery was 5.13 (0.45) minutes in patients with diabetes mellitus and <1 minute in controls. At seven minutes after release of the cuff CNAP was fully restored in the controls whereas in patients with diabetes mellitus CNAP had only reached 75.1 (4.1)% of its original amplitude. After onset of ischaemia it took 14.6 (1.9) minutes in patients with diabetes mellitus before the vibratory threshold was doubled, whereas this took 5.8 (0.8) minutes in controls. After release of the cuff half time for recovery of vibratory threshold was 8.8 (1.0) minutes in patients with diabetes mellitus and 2.6 (0.3) minutes in controls. Ten minutes after the cuff was released the threshold was still raised (2.0 (0.3)-fold) in the diabetes mellitus group, whereas it was normalised in controls. Among patients with diabetes mellitus the impaired recovery correlated with older age, higher HbA1c, and signs of neuropathy, but not with blood glucose. CONCLUSION: After ischaemia there is a delayed recovery of nerve conduction and the vibratory sensibility in patients with diabetes mellitus. Impaired recovery after ischaemic insults may contribute to the high frequency of entrapment neuropathy in patients with diabetes mellitus.

Adenosine for pain relief in a patient with intractable secondary erythromelalgia.

An unusual case is reported with severe erythromelalgia secondary to a sensorimotor polyneuropathy of immunological aetiology. The dominating symptoms were ongoing burning dysesthesia and pain in the legs, sustained thermal hyperalgesia and allodynia to pressure which produced intolerable pain on standing and walking. The primary pain-producing pathophysiology was apparently peripheral neurogenic inflammation with sensitization and excitation of nociceptors. The variable and progressive course prompted reassessments and successively amended multitargeted analgesic regimens. The most intensive bout of widespread pain and allodynia indicating secondary central sensitization was only controlled by adenosine treatment.

Motor cortex stimulation as treatment of trigeminal neuropathic pain.

A report is given on first experiences with motor cortex stimulation in 10 patients with different forms of neuropathic pain. Three of them had central pain as sequelae of cerebrovascular disease. In none of them did the stimulation provide pain relief. Two patients had pain from peripheral nerve injuries. One did not respond, but the other obtained about 50% pain relief. The remaining 5 patients with trigeminal neuropathy experienced definite pain relief varying between 60 and 90%. During test stimulation most patients had one or two short-lasting generalized seizures. But no one had any motor effects after permanent implantation. Motor cortex stimulation appears to be a new and promising possibility of pain treatment, especially in cases with trigeminal neuropathy, but many problems have yet to be solved, before a clear indication could be given.

Does a regional nerve block change cutaneous perception thresholds outside the anaesthetic area? Implications for the interpretation of diagnostic blocks.

The present study was performed on pain-free subjects and patients to analyse if local anaesthetics (LA) normally used for nerve blocks in the orofacial region resulted in generalised changes in cutaneous somatosensory perception thresholds outside the territory of the primarily blocked nerve. Five subjects received an intra-oral nerve block and 5 patients received epidural anaesthesia, serving as a reference group considering the larger amounts of LA used in this latter type of anaesthesia. No differences (after vs. prior to LA) were detected regarding thresholds to tactile, cold, warmth or heat pain stimuli in skin areas outside the regions directly blocked. This was also true for the difference limens between warm-cold thresholds. Our data do not indicate any generalised influence on tactile, thermal and pain perception thresholds in pain-free subjects.

Systemic mexiletine relieves chronic allodynialike symptoms in rats with ischemic spinal cord injury.

We have recently reported a chronic allodynialike symptom in rats after ischemic spinal cord injury. This pain-related behavior is resistant to a number of pharmacologic treatments, including morphine, clonidine, carbamazepine, baclofen, and muscimol. In the present report, we present evidence indicating that systemic mexiletine, a local anesthetic and antiarrhythmic agent, effectively relieves the allodynia-like symptoms at doses of 15 and 30 mg/kg in these rats without inducing major side effects. It is suggested that systemically applied mexiletine may be useful in treating central pain in patients with spinal cord injury.

Graded assessment and classification of impaired temperature sensibility in patients with diabetic polyneuropathy.

Thermal sensibility was quantitatively assessed in the feet of 46 diabetic patients. In subjects with sensibility deficits the perception threshold for warmth or cold, or of heat pain, was either increased or lost. Four stages of impaired thermal sensibility were defined, and a classification of dysfunction is proposed which could be useful in routine clinical examination of patients with diabetic polyneuropathy. The classification of impaired thermal sensibility correlated significantly with the results of a bedside screening examination aimed at describing the severity of the polyneuropathy in terms of its regional extent.

Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson's disease. One-year follow-up of first clinical trial.

Experimental studies in rodents show that beta-nerve growth factor can increase the survival, neurite outgrowth, and functional effect of grafts of adrenal chromaffin cells to the basal ganglia. We, therefore, have begun to investigate whether treatment with nerve growth factor might also increase the functional effect of autografts of adrenal medullary tissue in patients with Parkinson's disease. Previous studies have shown that stereotactic implantation of adrenal tissue pieces produces a transient functional improvement that lasts for a few months. This report describes a trial of grafting of adrenal chromaffin tissue into the putamen, supported by infusion of nerve growth factor. The patient is a 63-year-old woman with a 19-year history of Parkinson's disease, now complicated by on-off phenomena and drug-induced hyperkinesia, despite optimized medical management. The left adrenal gland was removed, and the medulla was dissected into 1- to 2-mm3 pieces in a solution containing nerve growth factor purified from mouse submandibular gland. Pieces were implanted in six tracts 3 to 4 mm from a previously placed cannula in the left putamen. Through the cannula, nerve growth factor was infused for 23 days for a total dose of 3.3 mg. Clinical assessment consisted of global ratings for rigidity and/or hypokinesia and for drug-induced hyperkinesia. Measures of gait and fine-motor control were also made. The motor readiness potential and auditory evoked potentials were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of lumbar spinal evoked potentials and their correlation with stimulation-induced paresthesiae.

In 7 awake patients with neuropathic lower extremity pain, spinal somatosensory evoked potentials (SEP) were elicited from the non-painful leg by electrical stimulation of the peroneal nerve and mechanical stimulation of the hallux ball. Recording was made epidurally in the thoraco-lumbar region by means of an electrode temporarily inserted for trial of pain-suppressing stimulation. In response to peroneal nerve stimulation, two major SEP complexes were found. The first complex consisted, as has been described earlier, of an initial positivity (P12), a spike-like negativity (N14), a slow negativity (N16) and a slow positivity (P23). The second complex consisted of a slow biphasic wave, conceivably mediated by a supraspinal loop. Both complexes had a similar longitudinal distribution with amplitude maxima at the T12 vertebral body. The SEP evoked by mechanical hallux ball stimulation had a relatively small amplitude, and there was no significant second complex. The relationship between stimulus intensity and SEP amplitude was negatively accelerating. The longitudinal distribution of spinal SEP was compared with the somatotopic distribution of paresthesiae induced by stimulation through the epidural electrode. It was found that stimulation applied at the level of maximal SEP generally induced paresthesiae in the corresponding peripheral region. Therefore, spinal SEP may be used as a guide for optimal positioning of a spinal electrode for therapeutic stimulation when implanted under general anesthesia. An attempt was made to record the antidromic potential in the peroneal nerve elicited from the dorsal columns by epidural stimulation. The antidromic response was, however, very sensitive to minimal changes of stimulus strength and body position of the patient, and was also contaminated by simultaneously evoked muscular reflex potentials. Thus, peripheral responses evoked by epidural stimulation appeared too unreliable to be useful for the permanent implantation of a spinal electrode for therapeutic stimulation.

Long-term relative survival rates after heart valve replacement.

The calculation and comparison of relative survival rates after interventional studies is a method that permits correction for important demographic variables, thereby adjusting for the "background mortality" in the general population. Long-term relative survival rates were analyzed in a consecutive series of 2,805 Swedish patients who, on the basis of clinical symptoms, underwent aortic valve replacement (n = 1,741), mitral valve replacement (n = 792) and double (aortic plus mitral) valve replacement (n = 272) between 1969 and 1983. The follow-up period, which closed August 1, 1985, included 100% of patients and covered 16,822 patient-years. Autopsy was performed in 75% of all deaths. The results underscore previously well known differences between the long-term survival after aortic valve replacement and mitral or double valve replacement, whereas no differences were noted between mitral and double valve replacement. Within the subgroup undergoing aortic valve replacement, analysis of relative survival rates disclosed a highly significant (p less than 0.001) difference between patients operated on for aortic stenosis and those operated on for aortic regurgitation, representing a mortality rate more than twice as high in the latter group. This difference was of much lesser magnitude when analyzed in the standard (actuarial) way. With a low (less than 2.5%) operative mortality rate for patients undergoing isolated elective aortic valve replacement in the current era and with an acceptable incidence of late valve-related death (5.2% at 10 years), these results may justify aortic valve replacement earlier in the course of chronic aortic regurgitation to prevent irreversible myocardial damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidurally recorded cervical spinal activity evoked by electrical and mechanical stimulation in pain patients.

Spinal SEPs to electrical and mechanical stimulation of the upper limb of the non-painful side in 7 pain patients were recorded from the cervical epidural space. In response to electrical stimulation of the median nerve, the longitudinal distribution of the spinal postsynaptic negativity (N13) along the cord had a distinct level of maximal amplitude at the C5 vertebral body. When recorded at increasing distances cranial or caudal to this level, the latency of N13 was successively prolonged, in agreement with a spread-out near-field generator in the dorsal horn. Similar patterns of distribution and levels of maximal amplitude were demonstrated for the N13 wave evoked by electrical stimulation of the ulnar and thumb nerves as well as by mechanical stimulation of the thumb ball. The amplitude ratios of the N13 waves evoked by electrical stimulation of the median nerve and the thumb nerves, and by mechanical stimulation of the thumb ball were 3.9 to 1.4 to 1. The slow positive wave (P18), which has been assumed to represent recurrent presynaptic activity, had a somewhat different distribution, with a lower maximal amplitude and a less marked falling off in amplitude along the cord, as compared to the N13 component. The initial presynaptic positivity (P10) appeared with an almost constant amplitude along the cord. Tactile stimuli produced responses with considerably longer latency and duration than those obtained with electrical stimulation. There seemed to be a non-linear relationship between the amplitude of the response and the depth of skin indentation. The presented data contribute a more detailed picture of epidurally recorded spinal SEPs than previous studies. They will serve as a reference for further analysis of SEPs evoked by stimulation of the affected side in pain patients, to explore whether the painful state is associated with altered SEPs before or after therapeutic intervention.

Heart valve replacement in septuagenarians.

Heart valve replacement was performed on 208 patients aged 70-80 years--aortic (AVR) in 172, mitral in 20 and both valves in 16 cases. All valves were of Björk-Shiley type, and all but six patients received maintenance oral anticoagulant therapy. The 100% follow-up comprised 744 patient-years (mean 4.0 years). The early mortality was 9.6% and was related to the complexity and urgency of surgery: After elective AVR for pure aortic stenosis the rate was 3.9%. Actuarial survival (early mortality excluded) was 79% at 5 years and 73% at 8 years overall, and 87% and 80% after AVR for stenosis. In the AVR group the relative (age- and -sex-adjusted) survival rate indicated a normalized survival pattern after the first year, with 87%, 'cure' rate (early mortality included), and the incidence of thromboembolism and of fatal bleeding complications equalled figures for younger patients. Mechanical heart valve implantation and maintenance anticoagulation thus seems to be safe treatment even in elderly patients, and eliminates need for valve re-replacement due to bioprosthetic degeneration.

Diagnostic value of quantitative sensory testing (QST) in carpal tunnel syndrome.

The initial sensory symptoms of carpal tunnel syndrome (CTS) are usually intermittent and the clinical neurological examination is often normal. The aim of the present study was to determine the rate of impairment of different somatosensory modalities in CTS by means of the following tests: vibrametry, tactile pulses, von Frey hairs, two-point discrimination (2-PD), graphesthesia and warm and cold perception thresholds. The material consisted of 33 hands with CTS from 22 patients. Each of the first 3 tests was abnormal with elevated thresholds in 17 CTS hands (52%), 2-PD was abnormal in 10 hands (30%), graphesthesia in 8 hands (24%), and warm and cold thresholds in only 5 hands (15%). There was an overlap so that at least one test was abnormal in 27 of the 33 CTS hands (82%). Thus, impairment of sensibility can be demonstrated in a majority of patients with CTS if more than one test is applied. Vibrametry and von Frey hairs are recommended instead of the commonly used 2-PD, since abnormality was more often revealed and since they are equally easy to apply. No individual test was sensitive enough to qualify as a diagnostic criterion when it was applied with the hand in resting position. A significant increase in both sensitivity and specificity can be expected for any test if it is combined with provocation, such as wrist flexion, as has been demonstrated for vibrametry.