The effect of observational learning on the development of central sensitization

Watching other people in pain may affect one’s own experience of pain. It is unknown whether it can also modulate secondary mechanical hypersensitivity. We have addressed this question in two experiments in healthy human volunteers. In experiment 1 we tested, on a large sample (N=83), five videos of a model demonstrating high or low pain during high frequency stimulation (HFS) of the skin, a procedure known to induce secondary mechanical hypersensitivity. The aim was to select the two videos rated with the highest and lowest expected pain and fear (high pain and low pain videos). Morevoer, we have explored the correlation between empathy and fear scores. In experiment 2 (N=44), two groups of participants were randomly allocated to watching either the low or the high pain video, and subsequently underwent HFS. The high pain video group reported increased pain during HFS. The two groups differed in the magnitude of secondary mechanical hypersensitivity after HFS, but the unpleasantness scores for mechanical stimulation after HFS, as well as spread of hyperalgesia were not statistically different. Empathy scores correlated positively with fear reports in experiment 1 but not experiment 2. Unexpectedly, we found higher scores of fear of pain for the high pain video only in experiment 1. In summary, observational learning of a model demonstrating high pain seems to have a stastistically significant but small effect on pinprick hypersensitivity. Its operating mechanisms remain partially elusive.

Spinal cord homeostatic plasticity gates mechanical allodynia in chronic pain

Central sensitization caused by disinhibition of spinal cord circuits is a key mechanism of mechanical allodynia in neuropathic pain. Despite intense efforts, the molecular mechanisms that drive disinhibition and induce allodynia after peripheral nerve injury remain unclear. Using the spared-nerve injury (SNI) model of allodynia, we here demonstrate that SNI induces disinhibition of spinal nociceptive circuits by triggering homeostatic synaptic plasticity. Specifically, SNI-triggered homeostatic plasticity suppresses the inhibitory outputs of parvalbumin-positive (PV+) interneurons that form synapses on both primary afferent terminals and excitatory interneurons, causing hyperactivation of the nociceptive pathway. Using genetic manipulations, we identified the retinoic acid receptor RARα as the key mediator of the homeostatic synaptic plasticity underlying this synaptic disinhibition. Deletion of RARα in PV+ neurons blocked SNI-induced spinal disinhibition, central sensitization, and allodynia. Moreover, deletion of RARα in spinal PV+ neurons or application of an RARα antagonist in the spinal cord prevented the development of SNI-induced mechanical allodynia. Together, our results reveal a molecular mechanism of neuropathic pain whereby homeostatic plasticity causes the mis-direction of tactile information flow to ascending nociceptive pathways following peripheral nerve injury.

The Spatial Extent of Pain Is Associated with Pain Intensity, Catastrophizing and Some Measures of Central Sensitization in People with Frozen Shoulder

The aim of this cross-sectional study was to explore the spatial extent of pain and its association with clinical symptoms, psychological features, and pain sensitization in people with frozen shoulder (FS). Forty-eight individuals with FS completed pain drawings (PDs) and reported their clinical symptoms including pain intensity (Visual Analogue Scale) and shoulder disability (Shoulder Pain and Disability Index). Moreover, pain sensitization measurements (pressure pain thresholds, temporal summation, conditioned pain modulation, and Central Sensitization Inventory (CSI)) were assessed. Psychological features were assessed by Pain Catastrophizing Scale (PCS) and Pain Vigilance and Awareness Questionnaire. Pain frequency maps were generated, Margolis rating scale was used for pain location, and Spearman correlation coefficients were computed. The mean (SD) pain extent was 12.5% (6.7%) and the most common painful area was the anterolateral shoulder region (100%). Women presented a more widespread pain distribution compared with men. Significant positive associations were obtained between pain extent and current pain intensity (rs = 0.421, p < 0.01), PCS (rs = 0.307, p < 0.05) and CSI (rs = 0.358, p < 0.05). The anterolateral region of the shoulder was the most common painful area in people with FS. Women with FS presented more extended areas of pain; and a more widespread distribution of pain was correlated with higher levels of pain, pain catastrophizing and pain sensitization.

Central Sensıtızatıon ın Axıal Spondyloarthrıtıs: An Exploratıve Study wıth Quantıtatıve Sensory Testıng and Clınıcal Scales

ABSTRACT Objective To evaluate the central sensitization (CS) and the related parameters in patients with axial spondyloarthritis (axSpA). Methods Quantitative sensory testing (QST) which consists of pressure pain threshold (PPT), temporal summation (TS), and conditioned pain modulation (CPM) were applied to the participants. Disease activity, functional status, sleep quality, pain, depression, and fatigue were assessed. Patients were divided as the ones with and without CS according to the central sensitization inventory (CSI) and the results were compared. Results One hundred patients and fifty controls were recruited. Sixty axSpA patients had CS. When QST results were compared between the patient and control groups, all PPT scores were found lower (p&lt;0.05) in patients. Regarding the comparison of the patients with and without CS, sacroiliac, and trapezius PPT scores were found lower in the patients with CS (p&lt;0.05). On the other hand, there was no significant difference in the mean TS scores (p&gt;0.05) between patients and controls, and in patients with and without CS. All investigated comorbidities were found to be significantly more frequent (p&lt;0.001) in the patients with CS. In regression analysis female gender, morning stiffness duration, CPM, depression, and fatigue were detected as related parameters with CSI scores. Conclusion CS and related comorbidities were found to be increased in axSpA patients. This increase should be taken into consideration in the management of these patients.