Pain
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Nocebo and placebo effects have been found to modulate several neurochemical systems, such as cholecystokinin, endogenous opioids, and endocannabinoids. Here we show that also the cyclooxygenase-prostaglandins pathway can be modulated by both nocebos and placebos. In fact, we found that negative expectation, the crucial element of the nocebo effect, about headache pain led to the enhancement of the cyclooxygenase-prostaglandins pathway, which, in turn, induced pain worsening. ⋯ We found a significant increase in headache and salivary prostaglandins and thromboxane in the nocebo group compared to the control group, suggesting that negative expectations enhance cyclooxygenase activity. In addition, placebo administration to headache sufferers at high altitude inhibited the nocebo-related component of pain and prostaglandins synthesis, which indicates that the cyclooxygenase pathway can be modulated by both nocebos and placebos. Our results show for the first time how nocebos and placebos affect the synthesis of prostaglandins, which represent an important target of analgesic drugs, thus emphasizing once again the notion that placebos and drugs may use common biochemical pathways.
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Pain is commonly assessed by subjective reports on rating scales. However, in many experimental and clinical settings, an additional, objective indicator of pain is desirable. In order to identify an objective, parametric signature of pain intensity that is predictive at the individual stimulus level across subjects, we recorded skin conductance and pupil diameter responses to heat pain stimuli of different durations and temperatures in 34 healthy subjects. ⋯ These results indicate that perceived pain is best reflected by the temporal dynamics of autonomic responses. Application of the regression model to an independent data set of 20 subjects resulted in a very good prediction of the pain ratings demonstrating the generalizability of the identified temporal pattern. Utilizing the readily available temporal information from skin conductance and pupil diameter responses thus allows parametric prediction of pain in human subjects.
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Comparative Study
Heritability of Nociception IV: Neuropathic pain assays are genetically distinct across methods of peripheral nerve injury.
Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified 5 genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional 9 assays of nociception and hypersensitivity, with the following goals: to replicate the previously identified 5 pain types; to test whether any of the newly added pain assays represent novel genetically distinct pain types; and to test the level of genetic relatedness among 9 commonly used neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the 2 previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. ⋯ In addition, 2 itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types.
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This study investigated change in the distribution of lumbar erector spinae muscle activity and pressure pain sensitivity across the low back in individuals with low back pain (LBP) and healthy controls. Surface electromyographic (EMG) signals were recorded from multiple locations over the lumbar erector spinae muscle with a 13×5 grid of electrodes from 19 people with chronic nonspecific LBP and 17 control subjects as they performed a repetitive lifting task. The EMG root mean square (RMS) was computed for each location of the grid to form a map of the EMG amplitude distribution. ⋯ PPT was lower in the LBP group after completion of the repetitive task compared to baseline (average across all locations: pre: 268.0±165.9 kPa; post: 242.0±166.7 kPa), whereas no change in PPT over time was observed for the control group (320.1±162.1 kPa; post: 322.0±179.5 kPa). The results demonstrate that LBP alters the normal adaptation of lumbar erector spinae muscle activity to exercise, which occurs in the presence of exercise-induced hyperalgesia. Reduced variability of muscle activity may have important implications for the provocation and recurrence of LBP due to repetitive tasks.