RESUMEN
OBJECTIVE: Evidence suggests that there is an association between chronic pain and disruption of the body schema. We tested the hypothesis in fibromyalgia syndrome (FMS). MATERIALS AND METHODS: We investigated distinct perceptual aspects of the body schema both in a sample of patients with FMS and in pain-free controls. Performances on the left/right judgment task were measured; tactile acuity was assessed by using the 2-point discrimination test. Furthermore, we evaluated sensations evoked by tactile stimulation with von Frey filaments to body parts that were experiencing pain. Anomalous sensations elicited by sensory-motor conflict (SMC) were also investigated. RESULTS: Patients with FMS showed inferior performance on the right/left judgment task, both in terms of correct matches (75.38% vs. 89.67%, respectively; P<0.05) and response time (2.58 s vs. 1.89 s, respectively; P<0.05). Effect sizes were large and very large, respectively. Two-point discrimination thresholds were significantly higher (P<0.05) in participants from the FMS sample (mean of 49.71 mm, SD: 12.09 mm) relative to controls (mean of 37.36 mm, SD: 7.81 mm). Nine of 14 participants with FMS, but no control participants, reported referred sensations upon tactile stimulation, including tingling, pins and needles, weight, and cramps. Referral sites included regions both adjacent and remote to stimulated sites. Patients with FMS scored across all items within the administered questionnaire addressing anomalous sensations on the mirror setup (Cohen d=1.04 to 2.42 across all items), and FMS patients perceived pain during the SMC (the required statistical power for it to be statistically significant was 96% and for it to be recognized as a difference of means in pain item). CONCLUSION: Our present findings suggest a disrupted body schema and propensity to experiencing anomalous somatosensory sensations during SMC in people with FMS.
Asunto(s)
Imagen Corporal/psicología , Discriminación en Psicología/fisiología , Fibromialgia/psicología , Percepción del Tacto/fisiología , Tacto/fisiología , Adulto , Femenino , Fibromialgia/fisiopatología , Humanos , Juicio/fisiología , Persona de Mediana Edad , Dimensión del Dolor , Umbral del Dolor/fisiologíaRESUMEN
The information from nociceptors is processed in the dorsal horn of the spinal cord by complex circuits involving excitatory and inhibitory interneurons. It is well documented that GluN2B and ERK1/2 phosphorylation contributes to central sensitization. Striatal-enriched protein tyrosine phosphatase (STEP) dephosphorylates GluN2B and ERK1/2, promoting internalization of GluN2B and inactivation of ERK1/2. The activity of STEP was modulated by genetic (STEP knockout mice) and pharmacological (recently synthesized STEP inhibitor, TC-2153) approaches. STEP(61) protein levels in the lumbar spinal cord were determined in male and female mice of different ages. Inflammatory pain was induced by complete Freund's adjuvant injection. Behavioral tests, immunoblotting, and electrophysiology were used to analyze the effect of STEP on nociception. Our results show that both genetic deletion and pharmacological inhibition of STEP induced thermal hyperalgesia and mechanical allodynia, which were accompanied by increased pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204)levels in the lumbar spinal cord. Striatal-enriched protein tyrosine phosphatase heterozygous and knockout mice presented a similar phenotype. Furthermore, electrophysiological experiments showed that TC-2153 increased C fiber-evoked spinal field potentials. Interestingly, we found that STEP(61) protein levels in the lumbar spinal cord inversely correlated with thermal hyperalgesia associated with age and female gender in mice. Consistently, STEP knockout mice failed to show age-related thermal hyperalgesia, although gender-related differences were preserved. Moreover, in a model of inflammatory pain, hyperalgesia was associated with increased phosphorylation-mediated STEP(61) inactivation and increased pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204)levels in the lumbar spinal cord. Collectively, the present results underscore an important role of spinal STEP activity in the modulation of nociception.