Rolf G. Hallin

Noradrenaline-evoked pain in neuralgia

&NA; We have tested the effects of cutaneous application of noradrenaline in 35 patients presenting with neuropathic pain. Depending on the outcome of sympatholytic interventions the patients were considered to have sympathetically maintained pain (SMP; n = 25) or sympathetically independent pain (SIP; n = 10). Iontophoretic application or cutaneous injection of noradrenaline into symptomatic skin aggravated pain and mechanical or thermal hyperalgesia in Symbol SMP patients. Results from differential nerve blocks suggested that noradrenaline‐induced ongoing pain and heat hyperalgesia were signalled by unmyelinated afferents, while touch‐evoked pain and cold hyperalgesia were signalled by myelinated afferents. In none of the remaining Symbol SMP patients, 10 SIP patients or 18 normal subjects did application of noradrenaline result in any appreciable increase of pain. A follow‐up of 12 patients (initially 9 SMP, 3 SIP) after 12–16 years showed that one individual (previously SMP) was healthy, while 3 patients still suffered from SMP and 8 from SIP. Of the 5 SMP patients who had noradrenaline‐induced pain at the initial examination, only 1 SMP patient still responded to noradrenaline with pain and hyperalgesia. Three other patients had changed to SIP and 1 individual was healthy. None of these 4 and none of the 7 initially noradrenaline‐unresponsive patients experienced pain to the noradrenaline challenge at follow‐up. Thus, cutaneous noradrenaline application can aggravate the pain in some, but not all SMP patients. The abnormal noradrenaline reaction can change over time as can the pain relieving effects of sympatholytic therapy. Symbol. No caption available Symbol. No caption available

Beneficial effects of ketamine in a chronic pain state with allodynia, possibly due to central sensitization

Allodynia is a well-known component of neuropathic pain resulting from injury to the nervous system. Clinical pain states with allodynia in connection with longstanding superficial wounds have, however, not been reported in the literature. In this case a chronic pain state developed in a previously healthy 17-year-old girl in and around a persistently suppurating appendectomy wound. There was no spontaneous pain but pronounced allodynia in the wound and in the surrounding skin. Quantitative thermal tests showed abnormal thresholds for several sensory modalities confirming abnormal processing of sensory input from the involved area. The pattern of sensory abnormalities evaluated with thermal testing changed transiently and the allodynia diminished during a phentolamine block. Since the pain responded poorly to opioids and ketamine has been reported to reduce allodynia, it was administered in a sub-dissociative bolus dose during wound dressing. The wound was essentially unchanged after treatment for 3 months but the allodynia and sensory aberrations had decreased significantly. We interpret these results as a de-sensitizing effect in the long term of repeated NMDA-receptor blockade by ketamine in a chronic pain state, with indications of central sensitization, partially maintained by sympathetic activity.

Physical training in Syndrome X: Physical training counteracts deconditioning and pain in Syndrome X

OBJECTIVES The aim of this study was to evaluate the effects of exercise training and body-awareness training in female patients with Syndrome X. BACKGROUND Patients with Syndrome X, defined as effort-induced angina pectoris, a positive exercise test and a normal coronary angiogram, suffer from a chronic pain disorder. We hypothesized that this disorder results in physical deconditioning with decreased exertional pain threshold. METHODS Twenty-six patients were randomly assigned to two training groups (A, B) and a control group (C). Group A (n = 8) started, after baseline measurements, with eight weeks of body-awareness training followed by eight weeks of exercise training on a bicycle ergometer three times a week for 30 min at an intensity of 50% of peak work rate. Group B (n = 8) performed only eight weeks of exercise training. Group C (n = 10) acted as controls without any intervention whatsoever. The effects on exercise performance, hormonal secretion, vascular function, adenosine sensitivity and quality of life were evaluated. RESULTS Body-awareness training did not change the pain response. The two training groups did not differ in effects of exercise training. Exercise capacity before training was below the gender- and age-matched reference range and improved by 34% with training to a level not different from the reference range. Onset of pain was delayed by 100% from 3 +/- 2 to 6 +/- 3 min (p < 0.05) while maximum pain did not change. Thus the pain-response-to-exercise curve was shifted to the right. Syndrome X patients showed a hypersensitivity to low-dose adenosine infusion compared to healthy age- and gender-matched controls (p < 0.0001) that did not change with exercise training. Endothelium-dependent blood flow increase was at baseline within reference range and tended to increase (p < 0.06) following training. In Group A the concentration of cortisol in urine decreased by 53% after body-awareness training (p < 0.05), and this change from baseline remained after physical exercise training (p < 0.05). A similar decrease occurred with only exercise training (Group B). CONCLUSIONS Physical deconditioning with lower exertional threshold for pain is a prominent feature in Syndrome X. Physical training in Syndrome X results in an increased exercise capacity with lesser anginal pain. We suggest physical training as an effective treatment in Syndrome X.

Spinal cord implantation of avulsed ventral roots in primates; correlation between restored motor function and morphology

Abstract Functional restitution following spinal cord implantation of avulsed ventral roots was assessed electromyographically and correlated with the morphology of the regenerated neural structures in primates. The C5–C8 ventral roots were avulsed from the spinal cord in seven Macaca fascicularis monkeys. In three animals the roots were immediately reimplanted into the ventrolateral part of the spinal cord. In two monkeys the avulsed roots were reimplanted with a delay of 2 months and in two control animals the roots were not reimplanted. There was substantial recovery of function after both immediate and delayed spinal cord implantation of the avulsed ventral roots. The population of neurons that had regenerated was larger than on the control side, indicating a rescue of cells after an immediate root implantation. Different functional types of neurons had been attracted to regrow axons to the implanted root as judged by their position in the ventral horn. Thus, neurons normally supplying antagonistic muscles, such as the triceps muscle, participated in the innervation of the biceps muscle. Functionally this deficient directional specificity was correlated to both spasticity and co-contractions among agonistic and antagonistic muscles. Occasional electromyographic signs of function occurred also in control animals where the avulsed roots had not been implanted. This recovery was found to depend on regrowth from the site of avulsion, within the pia mater among the leptomeningeal cells and to the avulsed roots. The acceptable functional dexterity regained due to corrective surgery is discussed in terms of neurotrophism and plasticity.

Influence of nerve lesions, strain differences and continuous cold stress on chronic pain behavior in rats

Abstract Three strains of rats (Sprague-Dawley, Wistar-Kyoto and Wistar-Spontaneously Hypertensive) underwent unilateral section of the sciatic nerve. Some of the rats were exposed to chronic cold (4°C) and others were housed in normal temperature (22°C). Significant differences were found among the three strains in the frequency and severity of autotomy and stress-related pain behavior observed over a 12 week period. The rats that were the most prone to hypertension performed the least autotomy. Common mechanisms involved in the control of blood pressure and pain may underly these observations.

Neurophysiological studies on patients with sutured median nerves: Faulty sensory localization after nerve regeneration and its physiological correlates

Abstract In this study 11 patients who had sustained a total traumatic transection of the median nerve at the wrist were investigated 5 to 12 years after nerve suture. Clinical and electrophysiological examinations were carried out, including conventional electromyography and electroneurography. In addition, percutaneous microelectrode explorations of the sutured nerves were done proximal to the site of injury. In all cases the functional neural recovery was incomplete as evaluated by conventional electrophysiological techniques. Primary skin afferent fibers reflecting activity in single regenerated myelinated fibers had virtually normal properties but their peripheral conduction velocity was abnormally slow. The identified units could be categorized as belonging to the four main types of mechanoreceptive units encountered in normal human glabrous skin. Multiunit responses from low-threshold mechanoreceptors had qualitatively normal characteristics but were typically evoked from abnormal types of receptive fields spread out in patches in reinnervated skin. The faulty sensory localization of cutaneous stimuli in nerve regeneration was possibly due to misinterpretation at central levels of signals deriving from misdirected outgrowing fibers innervating these skin patches.

Distribution of Human Pacinian Corpuscles in the Hand: A cadaver study

The subcutaneous distribution and number of Pacinian corpuscles were studied in ten fresh cadaver hands. They were found to cluster close to nerves and vessels at the metacarpophalangeal joints and the proximal phalanx. The total mean number in the hand was 300 (192–424). The percentage of the total was 44 to 60% in the fingers, 23 to 48% in the metacarpophalangeal area and 8 to 18% in the thenar and hypothenar regions. Corpuscles in palmar skin overlying the distal phalanx were smaller than receptors in the metacarpophalangeal area. The lowest density of corpuscles was along the nerves and vessels of the middle phalanx.

Stress-related pain behavior in rats with peripheral nerve injuries

&NA; The effects of cold stress were studied on rats with unilaterally sectioned sciatic nerves. Behaviors suggestive of pain occurred in a number of these animals. These behaviors vanished when removing the rats from the stressful environment. Some severely painful syndromes in man might in part be due to mechanisms similar to those underlying the described behaviors in rats.

Continuous naloxone administration via osmotic minipump decreases autotomy but has no effect on nociceptive threshold in the rat.

Abstract Rats with unilaterally sectioned sciatic nerves were continuously administered naloxone HCl (80 or 800 &mgr;g/h) or equivalent volumes of saline (1 or 10 &mgr;l/h) subcutaneously via osmotic minipumps over a 2 or 5 week period. Rats receiving 80 &mgr;g/h naloxone for 5 weeks exhibited significantly less self‐mutilation (autotomy) of the denervated foot than saline controls or rats receiving 80 &mgr;g/h naloxone for 2 weeks. The nociceptive threshold of intact rats infused with the same dose of naloxone was tested on a hot plate. In these animals there was no influence on the nociceptive threshold during naloxone administration for 1 week. Autotomy was also reduced in rats infused with 800 &mgr;g/h naloxone. The nociceptive threshold of intact rats infused with this dose of naloxone or an equivalent volume of saline (10 &mgr;l/h) was increased, suggesting that the presence of the larger osmotic pump caused analgesia.

Clustering of Pacinian corpuscle afferent fibres in the human median nerve

Abstract To further study the functional organisation of human peripheral nerves, the intrafascicular arrangement of afferent fibres supplying Pacinian corpuscles (PCs) was explored by percutaneous microneurography using thin-calibre, concentric needle electrodes. In normal adults, 20 PC afferents were identified in 13 recording sites. Low-amplitude (less than 30 µm) vibratory stimuli to the skin were applied with tuning forks oscillating at 128 Hz or 256 Hz and response patterns of individual PC units were studied. In many recording sites, two, sometimes even three, PC afferents with adjacent or overlapping receptive fields in the hand were clustered in the nerve. The observed incidence in the records containing a certain number of PC units was compared with the expected probability calculated according to the hypothesis that all nerve fibres are randomly organised in peripheral nerves. The results suggested that PC afferents are partially segregated in the nerve. In addition, PC afferents were neighbouring on slowly adapting type II (SAII) units and skin sympathetic activity in individual fascicles. SAII units often innervated the same skin area as PC units, but did not respond to vibration. The data provided additional information regarding the functional organisation of the human peripheral nerve and the mechanisms underlying the sense of vibration in man with special regard to population behaviour of neighbouring PC mechanoreceptors.