Human Studies

The American College of Rheumatology (ACR) 2016 criteria for fibromyalgia (FM) is recommended for use in primary and referral setting. However, neither the ACR 2016 nor its predecessor ACR 2010 criteria have been validated in a referral setting. We hypothesized that the presence of higher comorbidities in the referral care setting may affect the performance of the ACR 2016. All patients referred to a tertiary care hospital with widespread pain for more than 3 months were screened using (1) the ACR 2016 criteria and (2) by a blinded expert physician (using ACR 1990 criteria). Using the ACR 1990 as reference standard, the sensitivity and specificity were calculated. Also, concomitant depression (BPHQ: Brief Patient Health Questionnaire), anxiety disorder (GAD7: Generalized Anxiety Disorder-7) and alexithymia (TAS-20: Toronto Alexithymia Scale-20) were screened for using standardized instruments. Other central sensitization syndromes were also screened clinically. Of 147 patients (132 females; median age 36 [30-45] years, median symptom duration 4 [1-6] years), 112 met the ACR 1990 criteria while 93 met the ACR 2016 criteria. There was disagreement between the two criteria in 47 patients. The sensitivity and specificity of ACR 2016 were 71% and 60%, respectively. Patients diagnosed by ACR 2016 criteria alone, had higher GAD7 scores than those diagnosed by the ACR 1990 alone. However, BPHQ and TAS-20 did not differ between the groups. Patients diagnosed by the ACR 2016 criteria had a greater odds (OR 5.2 CI 1.3-21.7, p = 0.022) of having concomitant restless leg syndrome or post-traumatic stress disorder or chronic fatigue syndrome. The sensitivity/specificity of the ACR 2016 in tertiary settings matched those found in previous primary care-based studies. Thus, the ACR 2016 criteria are valid for use in the tertiary setting. However, patients diagnosed by only the ACR 2016 criteria (and not by the ACR 1990) have high probability of having another concomitant comorbidity.

Fibromyalgia is a complex, relatively unknown disease characterised by chronic, widespread musculoskeletal pain. The gut-brain axis connects the gut microbiome with the brain through the enteric nervous system (ENS); its disruption has been associated with psychiatric and gastrointestinal disorders. To gain an insight into the pathogenesis of fibromyalgia and identify diagnostic biomarkers, we combined different omics techniques to analyse microbiome and serum composition.

Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes.

Residual lower-limb pain after low back surgery (postsurgical sciatica) and complex regional pain syndrome (CRPS) involving a lower limb are separate conditions but may share some mechanisms (eg, tissue inflammation, neuroimmune disturbances, and central neuroplasticity). As adrenergically evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to postsurgical 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 postsurgical 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 4 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 postsurgical 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 neuroplastic changes are involved not only in the pathophysiology of CRPS but also in postsurgical sciatica. This may have treatment implications for patients with postsurgical sciatica.

The US National Pain Strategy focused attention on high-impact chronic pain and its restrictions. Although many interventions have been studied for chronic low-back pain, results are typically reported for heterogeneous samples. To better understand chronic pain and target interventions to those who most need care, more granular classifications recognizing chronic pain's impact are needed.