Low intensity vagal nerve stimulation lowers human thermal pain thresholds.

The effect of vagal nerve stimulation (VNS) on thermal pain sensation was studied in eight subjects who had vagal nerve stimulators surgically implanted for purposes of seizure control. Prior to their involvement in the study, all subjects had the intensity of their VNS (30 Hz, 0.5 ms, 1.0-2.75 mA) adjusted upwards until achieving their desired clinical effect of reduced seizures. Thermal pain thresholds were determined using a Medoc TSA-2001 with a thermode applied to the skin of the forearm. During VNS at settings 100% of those used clinically to control their seizures, subjects showed a statistically significant decrease in their thermal pain threshold of 1.1+/-0.4 degrees C. Acute effects of graded VNS on thermal pain thresholds were determined in seven of the subjects after cessation of chronic VNS. Two thermal threshold measurements were obtained while the subject received sham stimulation (0 mA intensity), during tactile control stimulation and during 30 s of VNS at intensities approximately 33, 66 and 100% of the settings utilized to control their seizures. Tactile control stimulation was provided by electrical stimulation of the skin of the ankle with the intensity adjusted by the patient to match the intensity of any sensations felt in the neck during VNS. Subjects were not aware of the settings employed. Their stimulator was adjusted with each trial and an ascending/descending ordering of intensity was utilized with an inter-trial interval of 2 min. Thermal pain thresholds were significantly decreased in relation to tactile control stimulation at all intensities of VNS tested with the greatest effect occurring at the 66% level. Subjects were also monitored non-invasively and hemodynamic responses to VNS were determined. No significant alterations in hemodynamic variables were observed. The findings of this human study are consistent with experiments in non-human animals which demonstrate a pro-nociceptive effect of low intensity VNS.

Analgesia for trauma and burns.

This article has described the physiologic impact of trauma- and burn-related pain as well as the effect of a clinician's choice of analgesic method, using the specific example of regional analgesia for pain caused by chest trauma. It has been observed that trauma exerts a holistic influence upon the organism, marshalling reflexes, multi-system physiologic stress responses, and psychologic responses--some adaptive and others maladaptive. There is reason to consider that timely analgesia can intervene in this dynamic process and interdict the establishment of a debilitated state. A key finding of these studies is that a report of pain relief may not be the best outcome measure since the choice of analgesic method(s) has a significant impact on the secondary effects of pain. Although extrapolated from studies of perioperative pain, findings do suggest that there may be a critical period of time during which the secondary effects of a painful stimulus may be attenuated or reversed. How long this period of reversibility exists has not been determined, so planning for the level and goals of analgesia intervention should occur early on. Analgesia should be viewed not only as a humanitarian gesture, but also a therapeutic maneuver with the goal being the early restoration of function and the mitigation of a chronic debilitated state. There is scattered evidence that regional analgesic techniques using local anesthetics have some advantages over other analgesic modalities, particularly in the trauma patient with pulmonary compromise; however, as with other medical interventions, one should develop a strategic plan of application which includes consideration of potential complications and side effects, in addition to the potential therapeutic effects. The traumatized body, as well as the attending physician, must deal with inflammation, the neurohumoral reaction, musculoskeletal reflex responses, and numerous other reactions designed to stabilize an acutely destabilized systemic entity. Multimodal analgesia, with the balanced use of systemic and regional medications, has given the best short- and long-term results in studies of postthoracotomy pain. The use of a similar combined plan for posttraumatic analgesia seems logical; however, many questions remain as yet unanswered. In particular, what are the optimal combinations of techniques/medications to employ to maximize analgesia and minimize secondary effects of trauma? Can an aggressive multimodal approach intervene effectively in the development of chronic pain states, and if so, for how long? What are the long-term benefits to be derived from making a significant impact on the stress response? Last, but not least, can analgesic interventions be shown to be cost-effective according to current societal pressures to reduce the cost of health care? These and other questions are not easy to answer. Trauma strikes, in a variable fashion, patients of all ages, with all forms of comorbidity, and is treated by a technology that continues to evolve. Previous research related to the effects of analgesic treatments has been hampered by the limitations that arise when isolated groups embark on vast projects with limited numbers of patients available. It is time for investigators at multiple centers to embark on coordinated efforts to address long-term questions related to trauma and the therapeutic efficacy of analgesia.

Neonatal capsaicin treatment abolishes the nociceptive responses to intravenous 5-HT in the rat.

The intravenous (i.v.) administration of serotonin (5-HT) to lightly pentobarbital-anesthetized rats is known to produce a triad of reflex cardiovascular responses, distinct afferent-mediated pseudaffective reactions, and a vagally mediated inhibition of the nociceptive tail-flick (TF) reflex consistent with 5-HT acting as a noxious stimulus. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating these responses. Lightly pentobarbital-anesthetized 16-week-old male Sprague-Dawley rats which had been treated as neonates (in the first 48 h of life) with capsaicin (50 micrograms/kg, s.c.) were compared to age-matched neonatal vehicle-treated controls. Whereas the i.v. administration of 5-HT produced a dose-dependent (6-96 micrograms/kg, i.v.) inhibition of the nociceptive TF reflex (ED50 = 48.1 +/- 11.3 micrograms/kg; n = 7) and distinct pseudaffective responses (usually by 24-48 micrograms/kg) in vehicle-treated rats, 5-HT (6-192 micrograms/kg, i.v.) failed to significantly alter TF latency or produce pseudaffective behaviors in the capsaicin-treated rats (n = 10). There was no difference in baseline TF latencies between the two groups. There were essentially no differences between vehicle- and capsaicin-treated rats with respect to the initial cardiopulmonary vagal afferent-mediated (Bezold-Jarisch reflex) decreases in heart rate and arterial blood pressure or the subsequent pressor phase. However, the magnitude of the late hypotensive phase was significantly greater in capsaicin-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)