The pathophysiology of the chronic pain following spinal cord injury (SCI) is unclear. In order to study it's underlying mechanism we characterized the neurological profile of SCI subjects with (SCIP) and without (SCINP) chronic pain. Characterization comprised of thermal threshold testing for warmth, cold and heat pain and tactile sensibility testing of touch, graphesthesia and identification of speed of movement of touch stimuli on the skin. In addition, spontaneously painful areas were mapped in SCIP and evoked pathological pain--allodynia, hyperpathia and wind-up pain evaluated for both groups. Both SCIP and SCINP showed similar reductions in both thermal and tactile sensations. In both groups thermal sensations were significantly more impaired than tactile sensations. Chronic pain was present only in skin areas below the lesion with impaired or absent temperature and heat-pain sensibilities. Conversely, all the thermally impaired skin areas in SCIP were painful while painfree areas in the same subjects were normal. In contrast, chronic pain could be found in skin areas without any impairment in tactile sensibilities. Allodynia could only be elicited in SCIP and a significantly higher incidence of pathologically evoked pain (i.e. hyperpathia and wind-up pain) was seen in the chronic pain areas compared to SCINP. We conclude that damage to the spinothalamic tract (STT) is a necessary condition for the occurrence of chronic pain following SCI. However, STT lesion is not a sufficient condition since it could also be found in SCINP. The abnormal evoked pain seen in SCIP is probably due to neuronal hyperexcitability in these subjects. The fact that apparently identical sensory impairments manifest as chronic pain and hyperexcitability in one subject but not in another implies that either genetic predisposition or subtle differences in the nature of spinal injury determine the emergence of chronic pain following SCI.

It is still unclear whether the quality of painful thermal sensation is determined only by conduction in specific, dedicated nociceptive channels (i.e. C or Adelta nociceptors) or whether it is a result of integrated activity in both nociceptive and non-nociceptive systems. To evaluate this question, we conducted quantitative and qualitative somatosensory testing in spinal cord injury subjects who suffered from partial or complete loss of thermal sensibility. Testing was performed in skin areas, below the level of the lesion, which were either lacking any thermal sensibility, lacking only one thermal sensation (either heat or cold) or having normal thermal sensations. We found that, in areas lacking any thermal sensibility, warm and cold stimuli produced a sensation of pricking pain, which had no thermal quality and was detected at significantly higher thresholds than in normal controls (48.5 +/- 1.8 and 9.7 +/- 5.1 degrees C for noxious heat- and noxious cold-induced pricking pain, respectively). Normal thermal pain sensations, consisting of normal perception of thermal quality and normal mean pain thresholds, were present both in normal skin areas (42.1 +/- 1.9 and 27.6 +/- 2.25 degrees C for heat and cold pain, respectively) and in areas in which only one thermal modality remained intact, when tested for that modality. Thus, testing for heat pain in areas in which only warm sensation was intact, or cold pain when only cold was intact produced normal qualities and thresholds of pain (42.8 +/- 3.4 and 24.4 +/- 6.2 degrees C for heat and cold pain, respectively). No spatial summation of pricking pain was observed, in contrast to the marked summation of heat pain in normal areas. In areas with only a single intact thermal modality, the quality of the perceived non-painful sensation was not determined by the thermal stimulus but by the intact modality (paradoxical sensation). Cold stimuli were perceived as warm in areas in which only warm sensation was preserved, and vice versa. A similar pattern was also seen for pain perception in areas with intact warm sensation. In these areas, both noxious heat and cold elicited a sensation of heat pain. No consistent pattern of heat-elicited pain was observed in areas in which only cold sensation was intact. These data suggest that the integrity of non-noxious thermal systems is essential for the normal perception of thermal pain, and that the subjective sensation of pain depends on the integration of information from nociceptive and non-nociceptive channels.

An experiment was designed to demonstrate the latent inhibition phenomenon in adult humans and to determine the effects of initial level of attention to the to-be-conditioned stimulus during a preexposure phase on subsequent learning. Results indicate that a strong latent inhibition effect can be obtained with adult humans. This effect occurs even though the preexposed stimulus is presented under severe conditions of inattention.

Systemic and intracerebroventricular administration of analgesic doses of morphine resulted in large increments of spontaneous multiple unit activity in the periaqueductal gray matter of the awake rat. Intracerebroventricular injection of methionine enkephalin gave analgesia in only 8 of 19 rats, but in all 8, and in no others, increased periaqueductal multiple unit firing was also seen. These findings support the view that the periaqueductal gray matter is actively involved in endogenous mechanisms of analgesia. A striking observation was that enkephalin caused electrographic and behavioral epileptic phenomena in most animals. This observation together with other recent findings suggests that endogenous enkephalin may play some role in epileptogenesis.

The ability of a painful stimulus to suppress pain in another, remote area (DNIC) has been intensely studied. However, the effect of the distance between the two painful stimuli and the attentional factors during the measurement of pain perception received minimal treatment. We evaluated the effect of these factors on DNIC and on the interaction between DNIC and spatial summation (SS) of pain. Subjects rated the intensity of a test stimulus (applied to one hand) alone and simultaneously with conditioning stimuli applied to four different locations; 5 and 30cm from the test stimulus on the same hand, the contralateral hand and contralateral leg. In each location, ratings were performed under three different instructions: summation, attention to test stimulus, attention to conditioning stimulus. The distance between the conditioning and test stimulus significantly affected pain perception (p<0.01) regardless of the instructions; SS occurred only at a distance of 5cm and DNIC occurred only in the remaining distances. DNIC's magnitude increased as the distance between the two stimuli increased (p<0.01). However, the instruction to summate attenuated DNIC and the DNIC instruction attenuated SS of pain. Attention to the conditioning stimulus induced a stronger DNIC than attention to the test stimulus (p<0.001). We conclude that (1) DNIC and SS of pain appear to be antagonistic processes. (2) DNIC is affected by the distance between two noxious stimuli and to a lesser extent, by attention. (3) The interaction between DNIC, SS and attention is complex and reflects the role of sensory-cognitive integration in pain perception.

Heat pain threshold is commonly considered to be an 'absolute' value, which is not dependent on the area stimulated. In contrast, suprathreshold heat pain sensation has been shown to be highly dependent on the area stimulated, with considerable spatial summation demonstrated both within and between dermatomes. The present study sought to reevaluate two major issues: (a) Whether nociceptive thresholds are, indeed, independent of stimulation area. (b) Whether the spatial summation of suprathreshold heat pain sensation is independent of threshold changes. Using noxious heat we evaluated nociceptive thresholds and perceived pain intensity for contact areas of 0.25, 2.25, 6.25 and 15.36 cm2. Our results show that considerable spatial summation of heat pain thresholds is obtained and an apparent spatial summation of perceived intensity can also be observed. However, these apparent changes in perceived pain intensity can be accounted for completely by the changes in noxious heat thresholds. Furthermore, when using a stimulus configuration in which stimulation area was increased without changing nociceptive threshold, no spatial summation of perceived pain intensity was seen. Our results suggest that the spatial summation of perceived heat pain intensity can be attributed to reduced heat pain threshold. Furthermore, our findings stress the importance of determining pain thresholds in studies examining the psychophysics of suprathreshold noxious stimuli.

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In the present study, we show that hypersensitivity to noxious thermal stimulation can be seen clearly in developing rats. Rats, at postnatal days 3, 6, 9, 12, 15, 21 and 90 were tested for reflex responsiveness to noxious heat, using tail withdrawal from hot water as the assay. Thermal nociceptive thresholds are considerably lowered, relative to adults, up to postnatal day 12. Thresholds were 39, 37.5, 40.8, 43.3, 46.5, 45.2 and 47.2 degrees C for the respective age groups. Enhanced sensitivity to suprathreshold noxious stimuli is seen in neonates up to postnatal day 15 (but not on day 9). Starting on day 21, sensitivity to noxious stimuli decreases with increasing age, as can be seen by the decrease in the slope of the temperature-response curve (system gain). Spinal transections at postnatal days 13, 17, 20, 60, or 100 did not produce a change in nociceptive thresholds in any of the age groups. In contrast, sensitivity to noxious stimulation (system gain) was enhanced by spinalization in rats 20 days of age or older. Based on these results we suggest that threshold elevation with increasing age most probably reflects changes in local spinal properties, while changes in responsiveness to suprathreshold noxious stimuli involves maturation of both spinal and descending supraspinal structures.