. Relationships between skin temperature and temporal summation of heat and cold pain. J Neurophysiol 90: 100 -109, 2003; 10.1152/jn.01066.2002. Temporal summation of heat pain during repetitive stimulation is dependent on C nociceptor activation of central N-methyl-D-aspartate (NMDA) receptor mechanisms. Moderate temporal summation is produced by sequential triangular ramps of stimulation that control skin temperature between heat pulses but do not elicit distinct first and second pain sensations. Dramatic summation of second pain is produced by repeated contact of the skin with a preheated thermode, but skin temperature between taps is not controlled by this procedure. Therefore relationships between recordings of skin temperature and psychophysical ratings of heat pain were evaluated during series of repeated skin contacts. Surface and subcutaneous recordings of skin temperatures revealed efficient thermoregulatory compensation for heat stimulation at interstimulus intervals (ISIs) ranging from 2 to 8 s. Temporal summation of heat pain was strongly influenced by the ISIs and cannot be explained by small increases in skin temperature between taps or by heat storage throughout a stimulus series. Repetitive brief contact with a precooled thermode was utilized to evaluate whether temporal summation of cold pain occurs, and if so, whether it is influenced by skin temperature. Surface and subcutaneous recordings of skin temperature revealed a sluggish thermoregulatory compensation for repetitive cold stimulation. In contrast to heat stimulation, skin temperature did not recover between cold stimuli throughout ISIs of 3-8 s. Psychophysically, repetitive cold stimulation produced an aching pain sensation that progressed gradually and radiated beyond the site of stimulation. The magnitude of aching pain was well related to skin temperature and thus appeared to be established primarily by peripheral factors. I N T R O D U C T I O NTemporal summation of pain occurs reliably when pulses of heat or electrical stimulation are delivered repetitively at rates as slow as one pulse in 3 s. Enhanced discharge of nocireceptive central neurons ("windup") can be observed under these conditions (Mendell 1966;Tommerdahl et al. 1998). Temporal summation for psychophysical and neural responses to heat is dependent on activation of unmyelinated (C) nociceptors and is dependent in part on activation of central N-methyl-D-aspartate (NMDA) receptors (Dickenson 1990;Graven-Nielsen et al. 2000;Price et al. 1994). Most investigations of heat pain summation have utilized triangular ramps from a Peltier device in constant contact with the skin. This method has the advantage of returning the skin to a baseline temperature between each ramping heat stimulus. However, because of limitations on the ramp speeds of Peltier thermodes (especially during down ramps), distinct first and second pain sensations that are attributable respectively to activation of myelinated (A-delta) and C nociceptors are not produced. Possibly because of inhibitory influe...

Irritable bowel syndrome (IBS) is a common intestinal ailment of which the pathophysiological mechanisms are not well understood. Most IBS patients demonstrate enhanced perception, visceral hypersensitivity, in response to distension of the gut lumen but there are conflicting results about changes in somatic sensitivity. This study focused on the possible contribution of abnormal pain sensitization due to positive feedback (vicious pain cycle) that affects somatic tissues due to viscero-somatic convergence. The specific objectives were to measure cutaneous thermal pain sensitivity along the segmental axis, including in dermatomes that are remote from the visceral pain focus. Pain sensitivity was probed with cutaneous thermal stimulation to the lower and upper extremities and the face in nine diarrhea-predominant IBS patients (diagnosed with ROME II criteria) and 12 healthy female controls. The stimuli were administered with a contact thermode, assuring that size of the stimulated area and stimulus duration were clearly defined and identical in all locations. Sensitization of IBS patients was not limited to symptomatic dermatomes (calf) but extended evenly across the body, including to the face (no sensitization gradient from foot to face). Also, the difference between IBS and control groups did not depend on the evoked pain intensity level, i.e. the degree of sensitization of IBS patients was similar near threshold (10% on the visual analog scale) and at higher intensities. Lastly, no correlation was found between IBS subjects' pain sensitivity of any of the three test sites and their ratings of spontaneous pain.

Background: Copper-associated hepatitis (CAH) is a well-documented chronic hepatic disease in dogs. In some breeds, the disease results from an inherited defect in copper metabolism. In others, it is unclear whether its acummulation is a primary or secondary condition. Reports of copper accumulation in dog breeds that are not genetically predisposed are increasing.Aim: To describe the epidemiology, clinical and laboratory findings, liver biopsy techniques, and treatment response in dogs with CAH.Methods: A retrospective study was performed, drawing upon medical records from CAH dogs at a Veterinary Referral Hospital in Paris, France. The diagnosis of CAH had been confirmed in these patients by positive rhodanine staining of hepatic tissue obtained through biopsy. Medical records were mined for the following data: age at presentation, sex, breed, chief presenting complaints, abdominal ultrasound (US) findings, and rhodanine staining pattern.Results: A total of 17 dogs were included in the study. Median age at presentation was 8-year old (4–11). No sex predisposition was found. Terriers (4/17) and German Shepherd Dogs (GSD, 3/17) were overrepresented. American Staffordshire Terriers and Beauceron had not previously appeared in case reports on CAH; two of each breed were identified in this study. Clinical signs of affected dogs were non-specific. An incidental identification of increased liverenzymes was observed in 5/17 dogs. A heterogeneous, mottled liver was frequently described (5/17) on abdominal US. Liver biopsies were performed by US-guided percutaneous approach in 10/17 dogs, laparoscopy and laparotomy in 6/17 and 1/17, respectively. The rhodanine staining pattern was centrilobular (zone 3) in 8/17 dogs and periportal (zone 1) in 3/17 dogs. The pattern was considered multifocal in 6/17 dogs.Conclusion: Increased liver enzymes may be the only clinical finding in dogs with copper-associated hepatitis, reflecting the silent progression of this disease. Centrilobular pattern of rhodanine staining was observed in the majority of cases suggesting the primary condition of the disease. Results of this study are consistent with the current literature, which reports that terriers and GSD are predisposed to CAH. This is the first  description of CAH in Beauceron and American Staffordshire Terrier dogs. Keywords: American Staffordshire Terrier, Beauceron, Copper-associated hepatitis, Liver biopsy, Rhodanine.

This study evaluated relationships between irritable bowel syndrome (IBS) pain, sympathetic dysregulation, and thermal pain sensitivity. Eight female patients with diarrhea-predominant IBS and ten healthy female controls were tested for sensitivity to thermal stimulation of the left palm. A new method of response-dependent thermal stimulation was used to maintain pain intensity at a predetermined level (35%) by adjusting thermal stimulus intensity as a function of pain ratings. Clinical pain levels were assessed prior to each testing session. Skin temperatures were recorded before and after pain sensitivity testing. The temperature of palmar skin dropped (1.5°C) when the corresponding location on the opposite hand of control subjects was subjected to prolonged thermal stimulation, but this response was absent for IBS pain patients. The patients also required significantly lower stimulus temperatures than controls to maintain a 35% pain rating. Baseline skin temperatures of patients were significantly correlated with thermode temperatures required to maintain 35% pain ratings. IBS pain intensity was not significantly correlated with skin temperature or pain sensitivity. The method of response-dependent stimulation revealed thermal hyperalgesia and increased sympathetic tone for chronic pain patients, relative to controls. Similarly, a significant correlation between resting skin temperatures and thermal pain sensitivity for IBS but not control subjects indicates that tonic sympathetic activation and a thermal hyperalgesia were generated by the chronic presence of visceral pain. However, lack of a significant relationship between sympathetic tone and ratings of IBS pain casts doubt on propositions that the magnitude of IBS pain is determined by psychological stress.

During the course of a psychophysical study of fibromyalgia syndrome (FMS), one of the subjects with a long history of headache and facial pain displayed an extraordinarily severe thermal allodynia. Her stimulus-response function for ratings of cutaneous heat pain revealed a sensitivity clearly beyond that of normal controls and most FMS subjects. Specially designed psychophysical methods showed that heat sensitivity sometimes increased dramatically within a series of stimuli. Prior exposure to moderate heat pain served as a trigger for allodynic ratings of series of normally neutral thermal stimulation. These observations document a case of breakthrough pain sensitivity with implications for mechanisms of FMS pain.