The journal of pain : official journal of the American Pain Society
-
Neurotoxicity is the limiting side effect of the anticancer agent oxaliplatin. A tangled panel of symptoms, sensory loss, paresthesia, dysesthesia, and pain may be disabling for patients and adversely affect their quality of life. To elucidate the morphologic and molecular alterations that occur in the nervous system during neuropathy, rats were daily injected with 2.4 mg kg(-1) oxaliplatin intraperitoneally. A progressive decrease in the pain threshold and hypersensitivity to noxious and nonnoxious stimuli were evidenced during the treatment (7, 14, 21 days). On day 21, morphometric alterations were detectable exclusively in the dorsal root ganglia, whereas the activating transcription factor 3 and neurofilament (heavy-chain) expression changed dramatically in both the nerves and ganglia. Inflammatory features were not highlighted. Interestingly, satellite cells exhibited signs of activation. Glial modulation was characterized in the spinal cord and brain areas involved in pain signaling. On the 21st day, spinal astrocytes increased numerically whereas the microglial population was unaltered. The number of glial cells in the brain differed according to the zone and treatment time points. In particular, on day 21, a significant astrocyte increase was measured in the anterior cingulate cortex, somatosensory area 1, neostriatum, ventrolateral periaqueductal gray, and nucleus raphe magnus. ⋯ These data highlight the relevance of glial cells in chemotherapy-induced neurotoxicity as part of the investigation of the role that specific brain areas play in neuropathy.
-
Observational Study
Pain sensitivity and autonomic factors associated with development of TMD: the OPPERA prospective cohort study.
Multiple studies report that individuals with chronic temporomandibular disorder (TMD) have enhanced sensitivity to experimental pain. Additionally, chronic TMD cases show altered autonomic function, including elevated heart rate and reduced heart rate variability. However, causal inferences regarding the association between TMD and pain sensitivity and autonomic function cannot be drawn from these cross-sectional observations. The prospective Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study examines whether measures of pain sensitivity or cardiac autonomic function provide predictive value in TMD incidence. A cohort of 2,737 initially TMD-free participants was followed for up to 5.2 years, during which time 260 developed first-onset TMD. Fourteen of 39 experimental pain measures produced significant hazard ratios, such that greater pain sensitivity was associated with greater TMD incidence. A single autonomic measure-heart rate at rest-was also associated significantly with greater TMD incidence. In contrast, using the same measures of pain sensitivity and cardiac autonomic function, we previously reported a larger group of variables that was significantly associated with chronic TMD in the OPPERA case-control study. Future studies should investigate whether premorbid pain sensitivity or autonomic function more specifically predicts risk of developing chronic TMD than first-onset TMD. ⋯ Our previous case-control studies showed that associations with both pain sensitivity and cardiac autonomic function are profound in chronic TMD cases. Here we show that some measures of enhanced pain sensitivity contribute modestly to the risk of developing TMD whereas autonomic dysregulation appears to confer little or no risk for TMD incidence.
-
Comparative Study
Comparative responsiveness of verbal and numerical rating scales to measure pain intensity in patients with chronic pain.
Verbal rating scale (VRS) and numerical rating scale (NRS) are regularly used to assess and monitor pain in chronic pain patients. Although the NRS has been generally preferred, limited comparative responsiveness evidence was reported. This study compared the responsiveness of VRS and NRS measuring current pain and investigated the influence of different references (ie, worst, least, average, and current pain or their composite) on the NRSs' responsiveness. Two hundred fifty-four chronic pain patients attended a 10-day pain self-management program and were assessed with two 6-point VRSs (assessing current pain) and four 11-point NRSs (assessing worst, least, average, and current pain) at pre- and posttreatment. A patient-reported rating of pain improvement was used as the criterion for standardized response mean and receiver operating characteristic curve analyses. Results showed that the VRSs and NRSs exhibited small responsiveness in all patients, but the magnitude of responsiveness became moderate to large in patients with improved pain. However, in patients with pain improvements, the NRS current pain item and composite score (made up of the 4 pain items) were found to have significantly larger responsiveness and greater discriminatory ability to detect the presence of improvement than other current pain VRSs and the NRSs assessing worst, least, and average pain. Potential implications for clinical practice are discussed. ⋯ This study shows that the current pain and composite NRSs were more responsive than the current pain VRSs and the NRSs measuring other individual pain references in patients with improved pain, undertaking a short-term, self-management program. The results help inform the selection of pain intensity measures in studies using similar types of intervention.
-
The temporal dynamics of the blood oxygen level-dependent (BOLD) signal, especially for painful stimulations, is not completely understood. In this study, the BOLD signal response to a long painful electrical stimulation (a continuous painful stimulation of 2 minutes) is directly compared to that of a short painful stimulation (four 30-second periods of painful stimulation interleaved with 30-second rest) in an effort to further probe the relationship between the temporal dynamics of the BOLD signal during constant-intensity pain stimulation. Time course analysis showed that both stimulation protocols produced 3 similarly timed peaks in both data sets, suggesting an early and delayed BOLD response to painful stimulation initiation, and a response related to stimulus termination. Despite the continuous stimulation, the BOLD signal returned to baseline in the 2-minute task. Even with this signal discrepancy, however, the activation maps of the 2 pain tasks differed only slightly, suggesting that the bulk of the activation is determined by the sharp rise in BOLD signal with stimulus onset. These findings imply that the BOLD signal response time course is not directly reflective of pain perception. ⋯ This article demonstrates that the BOLD signal for a painful stimulation contains multiple peaks and does not maintain the constant level during stimulation that is assumed in typical analysis. Although these dynamics should be accounted for in future studies because of their ability to confound results, their presence did not significantly alter the overall group maps.
-
To assess the longitudinal gray matter (GM) and white matter (WM) changes between repeated observations 1 year apart in a group of the early clinical stage of migraine patients without aura, and to explore the relationship of such structural changes with headache activity, we studied patients newly diagnosed with episodic migraine lasting 8 to 14 weeks. Optimized voxel-based morphometry and tract-based spatial statistical analyses were used to evaluate changes in GM and WM by using 3-dimensional T1-weighted and diffusion-tensor imaging, respectively. At the 1-year follow-up examination, GM reduction was observed in the dorsolateral and medial part of the superior frontal gyrus, orbitofrontal cortex, hippocampus, precuneus, and primary and secondary somatosensory cortices. No significant differences were found in the fractional anisotropy and longitudinal, radial, and mean diffusivity of WM in migraine patients without aura within a year. Negative results were found for the association between changes in headache activity parameters and GM. Our results indicated that the GM and WM changed in different pathophysiological conditions of migraine patients without aura. The WM probably evolves slowly in the course of migraine chronicity. ⋯ Our study found early involvement of GM reduction of sensory-discriminative brain regions in the pathologic process of migraine, but the WM did not exhibit significant changes in the same time interval. GM reduction in sensory-discriminative brain regions may characterize the pathophysiological features of migraine patients without aura in its early stage.