Human Studies

Measuring patients' experiences of health services has become an essential part of quality of care reporting and a means for identifying opportunities for improvement. This study aimed to evaluate change in patient experience in an interdisciplinary primary care program and to estimate the impact on patient experience of sociodemographic, function, pain and general health status, resource utilization, and process variables.

Neuropathic pain represents a primary detrimental outcome of spinal cord injury. A major challenge facing effective management is a lack of surrogate measures to examine the physiology and anatomy of neuropathic pain. To this end, we investigated the relationship between psychophysical responses to tonic heat stimulation and neuropathic pain rating after traumatic spinal cord injury. Subjects provided a continuous rating to 2 min of tonic heat at admission to rehabilitation and again at discharge. Adaptation, temporal summation of pain, and modulation profile (i.e., the relationship between adaptation and temporal summation of pain) were extracted from tonic heat curves for each subject. There was no association between any of the tonic heat outcomes and neuropathic pain severity at admission. The degree of adaptation, the degree of temporal summation of pain, and the modulation profile did not change significantly from admission to discharge. However, changes in modulation profiles between admission and discharge were significantly correlated with changes in neuropathic pain severity ( = 0.027; = 0.323). The modulation profile may represent an effective measure to track changes in neuropathic pain severity from early to later stages of spinal cord injury.

In western countries, lower back pain (LBP) is one of the most common disorders, experienced by more than 80% of the population. Chronic LBP due to disc degeneration has been linked to ongoing inflammatory processes in the disc and endplates. Pain effects the body in different ways, inducing a general stress response in which the body responds by releasing the stress hormone cortisol. Little is known about the impact of pain-induced stress on the progression of disc degeneration. Thus, the effects of cortisol on disc cells (DCs) and human mesenchymal stem cells (hMSCs) were explored in vitro with the objective of investigating the repercussions of cortisol on these cell types involved in de- and regenerative mechanisms of the disc. DC and hMSC pellet cultures were exposed to cortisol at two concentrations (150 and 300 ng/mL) for 28 days to simulate pain-induced stress. Cell viability, histological staining, and GAG DNA, along with apo-ptotic assays were conducted. Detection of OCT4, SOX9, IL-1R, and CXCR2 expressions was performed by immunohistochemistry. With cortisol treatment, restricted cell proliferation and less GAG production in both DCs and hMSCs were observed. Suppression of the differentiation and immunomodulatory efficacy of hMSCs was also detected. Moreover, elevated expressions of IL-1R and CXCR2 were detected in both cell types. To conclude, constant exposure to cortisol even at a physiological level enhanced pathological cellular processes in both DCs and hMSCs, which further jeopardized chondrogenesis. This suggests that cortisol resulting from pain-induced stress is a contributing component of intervertebral disc degeneration and may negatively affect regenerative attempts of the disc.

Representations of the body and peripersonal space can be distorted for people with some chronic pain conditions. Experimental pain induction can give rise to similar, but transient distortions in healthy individuals. However, spatial and bodily representations are dynamic, and constantly update as we interact with objects in our environment. It is unclear whether induced pain disrupts the mechanisms involved in updating these representations. In the present study, we sought to investigate the effect of induced pain on the updating of peripersonal space and body representations during and following tool-use. We compared performance under three conditions (pain, active placebo, neutral) on a visuotactile crossmodal congruency task and a tactile distance judgement task to measure updating of peripersonal space and body representations, respectively. Consistent with previous findings, the difference in crossmodal interference from visual distractors in the same compared to opposite visual field to the tactile target was less when tools were crossed than uncrossed. This suggests an extension of peripersonal space to incorporate the tips of the tools. Also consistent with previous findings, estimates of the felt tactile distance judgements decreased after active tool-use. In contrast to our predictions, however, we found no evidence that pain interfered with performance on either task when compared to the control conditions. Our findings suggest that the updating of peripersonal space and body representations is not disrupted by induced pain. That is, experiencing acute pain does not give rise to distorted representations of the body and peripersonal space that can be present in people with chronic pain conditions.

Voltage-gated sodium channel Nav1.9 is a threshold channel that regulates action potential firing. Nav1.9 is preferentially expressed in myenteric neurons, and small-diameter dorsal root ganglion (DRG) and trigeminal ganglion neurons including nociceptors. Recent studies have demonstrated a monogenic Mendelian link of Nav1.9 to human pain disorders. Gain-of-function variants in Nav1.9, which cause smaller depolarizations of RMP, have been identified in patients with familial episodic pain type 3 (FEPS3) and the more common pain disorder small fiber neuropathy. To explore the phenotypic spectrum of Nav1.9 channelopathy, here we report a new Nav1.9 mutation, N816K, in a child with early-onset episodic pain in both legs, episodic abdominal pain, and chronic constipation. Sequencing of further selected pain genes was normal. N816K alters a residue at the N-terminus of loop 2, proximal to the cytoplasmic terminus of transmembrane segment 6 in domain II. Voltage-clamp recordings demonstrate that Nav1.9-N816K significantly increases current density and hyperpolarizes voltage-dependence of activation by 10 mV, enabling a larger window current. Current-clamp recordings in DRG neurons shows that N816K channels depolarize RMP of small DRG neurons by 7 mV, reduce current threshold of firing an action potential and render DRG neurons hyperexcitable. Taken together these data demonstrate gain-of-function attributes of the newly described N816K mutation at the channel and cellular levels, which are consistent with a pain phenotype in the carrier of this mutation.