RESUMEN
Patients with functional pain disorders often complain of generalized sensory hypersensitivity, finding sounds, smells, or even everyday light aversive. The neural basis for this aversion is unknown, but it cannot be attributed to a general increase in cortical sensory processing. Here, we quantified the threshold for aversion to light in patients with fibromyalgia, a pain disorder thought to reflect dysregulation of pain-modulating systems in the brain. These individuals expressed discomfort at light levels substantially lower than that of healthy control subjects. Complementary studies in lightly anesthetized rat demonstrated that a subset of identified pain-modulating neurons in the rostral ventromedial medulla unexpectedly responds to light. Approximately half of the pain-facilitating "ON-cells" and pain-inhibiting "OFF-cells" sampled exhibited a change in firing with light exposure, shifting the system to a pronociceptive state with the activation of ON-cells and suppression of OFF-cell firing. The change in neuronal firing did not require a trigeminal or posterior thalamic relay, but it was blocked by the inactivation of the olivary pretectal nucleus. Light exposure also resulted in a measurable but modest decrease in the threshold for heat-evoked paw withdrawal, as would be expected with engagement of this pain-modulating circuitry. These data demonstrate integration of information about light intensity with somatic input at the level of single pain-modulating neurons in the brain stem of the rat under basal conditions. Taken together, our findings in rodents and humans provide a novel mechanism for abnormal photosensitivity and suggest that light has the potential to engage pain-modulating systems such that normally innocuous inputs are perceived as aversive or even painful.
Asunto(s)
Potenciales de Acción/fisiología , Tronco Encefálico/fisiopatología , Dolor Crónico/fisiopatología , Hiperalgesia/fisiopatología , Bulbo Raquídeo/fisiopatología , Neuronas/fisiología , Adulto , Anciano , Femenino , Humanos , Luz , Persona de Mediana Edad , Dimensión del Dolor/métodosRESUMEN
BACKGROUND: Results of previous studies suggest that ß-adrenoreceptor activation may augment pain, and that ß-adrenoreceptor antagonists may be effective in reducing pain, particularly in individuals not homozygous for the catechol-O-methyltransferase (COMT) high-activity haplotype. MATERIALS AND METHODS: Consenting patients admitted for thermal burn injury at participating burn centers were genotyped; those who were not high-activity COMT homozygotes were randomized to propranolol 240 mg/d or placebo. Primary outcomes were study feasibility (consent rate, protocol completion rate) and pain scores on study days 5 to 19. Secondary outcomes assessed pain and posttraumatic stress disorder symptoms 6 weeks postinjury. RESULTS: Seventy-seven percent (61/79) of eligible patients were consented and genotyped, and 77% (47/61) were genotype eligible and randomized. Ninety-one percent (43/47) tolerated study drug and completed primary outcome assessments. In intention-to-treat and per-protocol analyses, patients randomized to propranolol had worse pain scores on study days 5 to 19. CONCLUSIONS: Genotype-specific pain medication interventions are feasible in hospitalized burn patients. Propranolol is unlikely to be a useful analgesic during the first few weeks after burn injury.