The significance of A-delta and C fibres for the perception of synthetic heat.

Synthetic heat is a perception of strong, but not painful, heat arising when skin is stimulated by an alternating pattern of adjacent cold and warmth. This study examines the contribution of different classes of nerve fibres to this perception. In 40 subjects changes in synthetic heat and thermal perceptions were studied during a 30-min ischaemic nerve block in one reaction time, and one threshold determination task. Synthetic heat stimuli were described as hot or warm, but not as painful, and were preceded by a transient cold. Reaction times for synthetic heat stimuli did not differ from those for cold stimuli. Thresholds for synthetic heat and thermal stimuli were similar. During A fibre nerve block the perception of synthetic heat lost the cold component whereas the frequency of hot and warm descriptors did not change. The perception of cold stimuli changed, such that pure cold was replaced by dysaesthetic descriptors. Reaction times and thresholds for thermal and synthetic heat stimuli increased equally during the nerve block. It is concluded that the perception of synthetic heat most likely arises from the fusion of signals dependent on unmyelinated low threshold cold and warm receptors. It is not dependent on A-delta cold fibres, and a contribution of nociceptors is quite unlikely. The possibility of a psychological contribution at the perceptual level is discussed.

Quantitative and qualitative perceptual analysis of cold dysesthesia and hyperalgesia in fibromyalgia.

Somatosensory perception thresholds, perceived intensity, and quality of perceptions were assessed in 20 women with fibromyalgia syndrome (FMS) and in 20 healthy age-matched female controls. All patients and controls scaled perceived intensity and described perceived quality of randomized thermal (Thermotest) and tactile (von Frey filaments) stimulation. Perceived intensity was scaled by free-number magnitude estimation and interindividual comparability was accomplished by Master Scaling. Perceived quality was assessed by choosing verbal descriptors from a list. Thenar was used as a reference for each modality tested. All patients were able to reliably scale perceived intensity at thenar, as well as in pain-affected body areas. Perception thresholds for cold pain, heat pain, cold-pain tolerance and heat-pain tolerance were significantly lower in patients than controls. For cold and tactile stimulation, the master scaled perceived intensities were significantly higher in patients' pain-affected areas, whereas for warmth/heat stimulation, the intensities were significantly lower. In the qualitative perceptual analysis the most striking and significant finding was the aberration of cold-evoked perceptions in all patients: most stimuli in the range of 30-10 degrees C were reported as heat or other paresthetic or dysesthetic perceptions. The perceptual quality of warmth, and of touch, did not differ from the controls. Another aberration was observed in the nociceptive range of thermal and of tactile stimulation as significantly more frequent pain-related descriptors than in controls. This indicates a general nociceptive facilitation in addition to the lower thermal pain thresholds. The combination of cold hyperesthesia, cold dysesthesia, and multimodal hyperalgesia suggests a selective pathophysiology at a particular level of integration, possibly in the insular cortex. It is suggested that the aberrations revealed by the supraliminal sensory evaluation may be generic for FMS. Particularly, the aberrations established in all patients for perceived quality and intensity in the cold sensory channel may be an additional diagnostic criterion.

Prolonged relief of neuralgia after regional anesthetic blocks. A call for further experimental and systematic clinical studies.

Thirty-eight consecutive patients with neuralgia after peripheral nerve injury were treated with one or two series of peripheral local anesthetic blocks. All patients experienced an initial total relief of ongoing pain for 4-12 h. Evoked pain (hyperalgesia or allodynia), which occurred in 17 patients, was blocked simultaneously with the spontaneous pain. In 18 patients the analgesia outlasted the conduction block and there was a period of complete pain relief of 12-48 h in 13 patients and of 2-6 days in the other 5. In 8 patients there was a second phase of analgesia of 4 h to 6 days duration occurring within 12 h of pain recurrence. Thus, mono- or biphasic prolonged complete analgesia occurred in 25 out of 38 patients. A prolonged analgesia may be the result of a central action of the local anesthetic at the spinal level after intra-axonal incorporation and centripetal axoplasmic transport. To test this hypothesis, an experimental study with [3H]lidocaine was performed in 6 rats. The radioactive local anesthetic was injected into one hind limb foot with the other side serving as a control. Tissue samples from the peripheral nerve, nerve root and the lumbosacral spinal cord segment were analyzed for radioactivity using a scintillation counter technique at various time intervals after the [3H]lidocaine injection. There was a low grade of activity in all samples and no difference between the test side and the control side. Thus these experiments provided no evidence in support of this hypothesis. Various alternative peripheral and central mechanisms are discussed. Further studies specifically directed to these alternatives and with longitudinal controls are prompted.

Central dysesthesia syndrome in spinal cord injury patients.

We have described 13 spinal cord injury patients with a complaint of diffuse, ongoing dysesthesias below the level of the lesion, which are burning in quality, and usually functionally limiting. Quantitative sensory and neurophysiological testing revealed relative preservation of the dorsal column functions in comparison to absence of spinothalamic system mediated functions. On the basis of these findings, we are speculating that such an imbalance between the spinothalamic and dorsal column systems is the main underlying mechanism of dysesthesias as a central nervous system misinterpretation of residual peripheral input.

The analgesic effect of tocainide in trigeminal neuralgia.

Tocainide is a derivative of lidocaine with anti-arrhythmic action and, unlike lidocaine, can be used for oral treatment. Tocainide was alternatively with carbamazepine given to 12 patients with trigeminal neuralgia in a double-blind cross-over study for 2 weeks. The analgesic effect was estimated each day by the patients using a 0-10-point scale summarizing the frequency and severity of the attacks. The similarity in analgesic effect of the two drugs was striking. A possible analgesic mechanism could be that tocainide blocks the sodium channels in the hyperexcitable nerve membranes in the pain-producing foci in trigeminal neuralgia.

Increase of vibration threshold during wrist flexion in patients with carpal tunnel syndrome.

The most prominent symptoms of carpal tunnel syndrome (CTS) are sensory, with intermittent numbness, paraesthesiae and pain in the fingers innervated by the median nerve. No consistent signs are found by neurological examination, however. Conventional sensibility tests are positive in only about 50% of the cases. This applies also to quantitative tests such as measurement of the perception threshold for vibration (VT). In an attempt to find a more reliable indication and improve the diagnostic value of sensory testing, determination of VT was combined with provocation by means of wrist flexion. In a patient group with neurophysiologically verified CTS, all patients exhibited an increase to at least twice the VT value in the fingers innervated by the median nerve. No increase was seen in the little finger or in a control group of patients with digital paraesthesiae but with normal neurophysiological findings. It is concluded that VT measurements during wrist flexion can be used as a supplementary or alternative diagnostic criterion to indicate that the nerve dysfunction is located in the carpal tunnel.

Pressure-pain threshold in human temporal region. Evaluation of a new pressure algometer.

A hand-held pressure algometer with a pressure sensitive strain gauge at the tip was used to measure the pressure-pain threshold (PPT) in the temporal region of healthy volunteers. Various sizes of circular tips and various application rates were tested before selecting an area of 0.5 cm2 and a constant application rate of 0.68 N X sec-1 for future use. A highly significant correlation was found between PPT values obtained from the two sides (of the head) (P less than 0.001) and between PPT values obtained with a 3-week interval (P less than 0.001). In a series of 50 immediate consecutive measurements in the same individual, the mean PPT was 171 kPa (N = 6, 2 S.D. 24%). The mean relative change in PPT after a 3-week interval was 0 +/- 51% (N = 11, 2 S.D.). In the course of 5 repeated determinations at weekly intervals there was a significant increase in PPT (ANOVA, P less than 0.05). Subcutaneous lignocaine significantly elevated PPT compared to placebo. Due to the high inter-individual variation, determinations of PPT for group comparisons should include rather large population samples, whereas in paired studies, the intra-individual variation allows the investigation of much smaller groups (10-20 subjects). It is our experience that the pressure algometer is easy to operate in the hands of a skilled laboratory assistant.

The effect of systemic tocainide, lidocaine and bupivacaine on nociception in the rat.

The analgesic properties of systemically administered tocainide, a primary amine congener of lidocaine with a longer duration of action, were examined in rats. Significant antinociception, as assayed on the hot-plate test, was observed after i.p. tocainide at doses below toxic levels. No antinociception was seen with non-toxic doses of lidocaine or bupivacaine.

Vascular participation in deep cold pain.

As the magnitude of cold pain probably depends on blood flow and thus on internal limb temperature, the activated nociceptors should be close to or within the walls of veins. This hypothesis was tested by injecting small quantities (20 ml) of cold saline into an empty vein of the hand in 16 subjects. Saline temperatures below 26 degrees C elicited pure cold sensations whereas temperatures below 20 degrees C evoked both cold and pain sensations. Pain was mainly described as deep and it tended to radiate along the veins. With saline of 5 degrees C the pain tolerance level of several subjects was reached. Pain always appeared after cold and it disappeared before or together with cold. The results can be explained on the basis of two types of vascular receptors: a sensitive specific cold receptor and a nociceptor with a threshold around 20 degrees C.

Are the endorphins active in clinical pain states? Narcotic antagonism in chronic pain patients.

To test the possibility of endorphin release in clinical pain states naloxone was given, alternate with saline, in a double-blind study to 10 patients with chronic neuralgia or low back pain. There was no significant alteration of the levels of spontaneous pain or heat pain thresholds. The results suggest that the endorphin system does not offer protection of any importance in chronic pain.

The effect of dorsal column stimulation on the nociceptive response of dorsal horn cells and its relevance for pain suppression.

The effect of single and repetitive electrical stimulation of the dorsal columns on cells in laminae IV and V of the ipsilateral dorsal horn at S1 was examined in spinalized cats. About two-thirds of the cells responded to thermal nociceptive cutaneous stimulation and of these most responded also to low threshold mechanical stimulation. The other one-third of the cells were innervated by mechanoreceptors including type I or Haarscheiben. A single shock to the dorsal columns typically caused short latency activation of the cells, followed by inhibition lasting about 100 msec. Several minutes of repetitive dorsal column stimulation (DCS) at 3 Hz or 50 Hz had no prolonged effect on about two-thirds of the cells. The rest of the cells were less responsive for up to 30 min after the cessation of 50 Hz. Assuming that the studied interneurons have a pain-mediating function, the results indicate that some cumulative and poststimulatory DCS suppression of pain may be ascribed to spinal mechanisms. The more effective and longer lasting suppression produced by DCS in pain patients would, however, be dependent on other types of interneurons, on suprasegmental loops and/or on effects on pathophysiological mechanisms which may be operative in the chronic pain state. The lack of cumulative inhibition in most of the cells in this study is compatible with the previous observation of a retained perception of acute pain during DCS in man.