Human Studies

The DSM-5 diagnosis 'opioid use disorder' (OUD) was established to better describe and detect significant impairment or distress related to opioid use. There is no data on rates of OUD in chronic non-cancer pain (CNCP) in European countries. Therefore, our objective was to screen patients in specialised pain centres for signs of OUD.

Residual lower limb pain after low back surgery (post-surgical sciatica) and complex regional pain syndrome involving a lower limb (CRPS) are separate conditions, but may share some mechanisms (e.g., tissue inflammation, neuro-immune disturbances and central neuro-plasticity). As adrenergically-evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to post-surgical sciatica was investigated in this study. Immunohistochemistry was used to identify α1-adrenoceptors (α1-AR) on nerve fibres and other targets in the affected and contralateral skin of 25 patients with post-surgical sciatica, and α1-AR expression was investigated in relation to pain and pinprick hyperalgesia after intradermal injection of the α1-AR agonist phenylephrine. In addition, quantitative sensory testing was performed on all four limbs and on each side of the forehead. α1-AR expression was greater in keratinocytes (but not blood vessels or nerve fibres) in the symptomatic than contralateral leg, and dermal nerve fibre density was reduced in both legs. However, distal adrenergic involvement in pain in post-surgical sciatica seems unlikely, as neither heightened α1-AR expression in keratinocytes nor reduced dermal nerve fibre density were associated with pain or hyperalgesia to intradermal phenylephrine injection. Sensitivity to pressure-pain, pinprick and cold-pain was greater in the ipsilateral than contralateral forehead of the entire cohort, but sensory disturbances were most pronounced in patients with additional CRPS-like features. Together, these findings suggest that bilateral distal neuropathy and central neuro-plastic changes are involved not only in the pathophysiology of CRPS but also in post-surgical sciatica. This may have treatment implications for patients with post-surgical sciatica.

Tumor growths, migraine headaches, and other health-related complications reported in patients with neurofibromatosis type 1 (NF1) are often associated with pain. Thus, this study sought to describe and quantify the pain experience in children and young adults with NF1. Surveys were administered to 49 participants (28 children and 21 adults), ages 8 through 40 years. The survey included the Numeric Rating Scale 11 (NRS11) to assess pain intensity and the Patient Reported Outcomes Measurement Information System (PROMIS) to assess pain interference. A supplemental survey was created to measure pain frequency, chronicity, quality, and location. Results suggest pain is not only present in 55% of the cohort, but that it can begin at early ages. Pain was chronic in 35% of participants, with 41% reporting the use of medication to manage pain symptoms. Common sources of pain included migraine headaches and NF-related tumors. Pain was described as having neuropathic features (i.e., burning, tingling, numbness, or itching), and was localized to the head, back, and extremities. Further, subsets of participants reported moderate-to-severe pain intensity, high frequency of pain, and interference of pain in daily activities. Continued investigation of the pain experience in a multisystem disorder, such as NF1, remains essential to providing guidance in the setting of complex pain management.

The effectiveness of cognitive strategies to attenuate pain has been reported in various behavioural studies, however the underlying neuronal mechanisms are only now beginning to be understood. Using a 7 T fMRI, we investigated three different pain attenuation strategies in 20 healthy subjects via: (a) non-imaginal distraction by counting backwards in steps of seven; (b) imaginal distraction by imagining a safe place; and (c) reinterpretation of the pain valence (reappraisal). Although we found considerable variability in the performances, all strategies exhibited a significant relief of pain compared to an unmodulated pain condition. Our finding argues against a subject's potential predisposition for a certain attenuation approach, as some of the subjects performed well on all attenuation tasks yet others performed low on all attenuation tasks. We further investigated the variability of performance within-subjects and explored the cortical regions that contribute to successful single attempts of pain attenuation at trial level. For each of the three tasks, we found a different pattern of brain activity that reflects the performance of pain attenuation. The more successful trials are related to reduced activity of different parts of the insular cortex. Behavioural data suggest that distraction is the preferable cognitive strategy to modulate pain perception. For three different cognitive strategies we revealed brain regions that are suggested to reliably modulate the perception of pain. The findings could be of utmost benefit for future attempts to integrate neuroscientific techniques into the treatment of pain. Further studies are necessary to investigate whether the present results are transferable to patients as an essential part of the multimodal therapy for chronic pain. These patients may also benefit from additional neurofeedback techniques by combining the strategies with the cortical feedback in order to modulate pain-related brain activity.

The goal of this study was to refine clinical MRS to optimize performance and then determine whether MRS-derived biomarkers reliably identify painful discs, quantify degeneration severity, and forecast surgical outcomes for chronic low back pain (CLBP) patients.