COVID-19: A Potential Trigger for Thyroid Dysfunction.

Subacute thyroiditis (SAT) is a self-limiting thyroid dysfunction of viral origin. Relatively little is known about its occurrence in SARS CoV-2 infected COVID-19 patients. Herein, we report a case of SAT in a 58-year-old patient that was apparently triggered by infection with SARS CoV-2. Clinical, laboratory and imaging features of the patient are presented. The patient was vitally stable with a slightly tender and warm thyroid gland, which was painful on swallowing. His free thyroxine (FT4) was elevated, thyroid stimulating hormone (TSH) was below normal and free triiodothyronine (FT3) was in the physiological range. Previous thyroid exam conducted as a part of routine annual physical checkup was normal. The patient was put on prednisolone and recovered completely within three weeks.

microRNA let-7i-5p mediates the relationship between muscle fat infiltration and neck pain disability following motor vehicle collision: a preliminary study.

Persistent neck-pain disability (PNPD) is common following traumatic stress exposures such as motor vehicle collision (MVC). Substantial literature indicates that fat infiltration into neck muscle (MFI) is associated with post-MVC PNPD. However, little is known about the molecular mediators underlying this association. In the current study, we assessed whether microRNA expression signatures predict PNPD and whether microRNA mediate the relationship between neck MFI and PNPD. A nested cohort of 43 individuals from a longitudinal study of MVC survivors, who provided blood (PAXgene RNA) and underwent magnetic resonance imaging (MRI), were included in the current study. Peritraumatic microRNA expression levels were quantified via small RNA sequencing, neck MFI via MRI, and PNPD via the Neck Disability Index two-weeks, three-months, and twelve-months following MVC. Repeated measures regression models were used to assess the relationship between microRNA and PNPD and to perform mediation analyses. Seventeen microRNA predicted PNPD following MVC. One microRNA, let-7i-5p, mediated the relationship between neck MFI and PNPD. Peritraumatic blood-based microRNA expression levels predict PNPD following MVC and let-7i-5p might contribute to the underlying effects of neck MFI on persistent disability. In conclusion, additional studies are needed to validate this finding.

Dry Cupping Therapy for Improving Nonspecific Neck Pain and Subcutaneous Hemodynamics.

CONTEXT: Dry cupping therapy is a noninvasive treatment commonly used to reduce pain and promote the healing process in various populations, including those with nonspecific neck pain; however, no data are available to support most of this method's true physiological benefits. OBJECTIVE: To determine if dry cupping therapy decreased pain and increased subcutaneous blood flow compared with sham cupping and control conditions. DESIGN: Controlled laboratory study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 32 participants (age = 22.5 ± 2.8 years, height = 173.3 ± 10.1 cm, mass = 76.6 ± 18.7 kg) with self-reported nonspecific neck pain. INTERVENTION(S): We used dry cupping and sham cupping interventions and a control condition. For the dry cupping intervention, 1 stationary cup was placed directly over the most painful area for 8 minutes. The sham cupping intervention followed the same procedures as the dry cupping intervention except a sham cup was applied. For the control condition, participants received no treatment. MAIN OUTCOME MEASURE(S): Subjective pain intensity (visual analog scale); pain-pressure threshold; subcutaneous hemodynamics, including superficial and deep oxygenated, deoxygenated, and total hemoglobin levels; and tissue saturation index. RESULTS: We observed differences in the visual analog scale score and the superficial and deep oxygenated and total hemoglobin levels (P values ≤ .002) immediately postintervention compared with baseline. Post hoc tests revealed that the dry cupping group had less pain than the sham cupping and control groups and higher superficial and deep oxygenated and total hemoglobin levels (P values ≤ .008). No differences were found between baseline and 24 hours postintervention. CONCLUSIONS: A single session of dry cupping therapy may be an effective short-term treatment method for immediately reducing pain and increasing oxygenated and total hemoglobin levels in patients with nonspecific neck pain.

The immediate effects of cervical spine manipulation on pain and biochemical markers in females with acute non-specific mechanical neck pain: a randomized clinical trial.

Study Design: Randomized clinical trial with pre-test, post-test control group design. Objectives: To examine the immediate effects of cervical spinal manipulation (CSM) on serum concentration of biochemical markers (oxytocin, neurotensin, orexin A, and cortisol). Background: Several studies have found an association between spinal manipulation (SM) and pain perception. However, the mechanism by which SM modulates pain remains undefined. Methods: Twenty-eight female subjects with non-specific mechanical neck pain were randomly assigned to one of two interventions (CSM versus sham CSM). Blood samples were drawn before and immediately after the respective interventions. Oxytocin, neurotensin, orexin A, and cortisol were measured from the blood and serum using the Milliplex Map Magnetic Bead Panel Immunoassay on the Luminex 200 Platform. Results: In the CSM group, there were significant increases in pre- versus post-manipulation mean oxytocin (154.5 ± 60.1 vs. 185.1 ± 75.6, p = .012); neurotensin (116.0 ± 26.5 vs.136.4 ± 34.1, p < . 001); orexin A (52.2 ± 31.1 vs. 73.8 ± 38.8, p < .01) serum concentration; but no significant differences in mean cortisol (p = .052) serum concentration. In the sham group, there were no significant differences in any of the biomarkers (p > .05). Conclusion: The results of the current study suggest that the mechanical stimuli provided through a CSM may modify neuropeptide expression by immediately increasing the serum concentration of nociception-related biomarkers (oxytocin, neurotensin, orexin A, but not cortisol) in the blood of female subjects with non-specific mechanical neck pain.

The Influence of Treatment Expectations on Clinical Outcomes and Cortisol Levels in Patients With Chronic Neck Pain: An Experimental Study.

BACKGROUND: The role of contextual factors like pre-existing treatment expectations has been established. However, the effect of verbally delivered treatment expectations in patient-therapist communication has not been considered, nor has the role of cortisol changes within the placebo/nocebo response in people with chronic neck pain. OBJECTIVE: To examine the effect of verbally delivered treatment expectations on clinical outcomes in physical therapy practice and to determine if changes in cortisol levels are associated with changes in neck pain and disability. METHODS: Eighty-three patients with chronic neck pain were randomly allocated to 3 different verbally delivered expectations (positive, negative, neutral) during physical therapy interventions. MAIN OUTCOME MEASURES: salivary cortisol, pain and disability, and cervical range of motion. RESULTS: Pain significantly improved in the positive (P < 0.001) and neutral (P < 0.001) expectations groups. For salivary cortisol levels, a significant increase was observed in response to treatment in the neutral (P = 0.045) and negative (P < 0.001) expectations groups. No significant correlations were found between changes in salivary cortisol levels and the change in pain in the neutral and negative expectations groups. CONCLUSIONS: Physical therapists treating people with chronic neck pain should be attentive when communicating the expected treatment effects to their patients. Whereas verbally delivered positive or neutral expectations may be beneficial for pain-related measures, giving negative expectations may result in a lack of a treatment response on pain. Cortisol levels increased in response to verbally delivered neutral and negative expectations, in the absence of a nocebo effect. This questions the presumed role of cortisol in the nocebo effect.

Vitamin D and ferritin correlation with chronic neck pain using standard statistics and a novel artificial neural network prediction model.

AIM: Despite the high prevalence of chronic neck pain, there is limited consensus about the primary etiology, risk factors, diagnostic criteria and therapeutic outcome. Here, we aimed to determine if Ferritin and Vitamin D are modifiable risk factors with chronic neck pain using slandered statistics and artificial intelligence neural network (ANN). METHODS: Fifty-four patients with chronic neck pain treated between February 2016 and August 2016 in King Abdullah University Hospital and 54 patients age matched controls undergoing outpatient or minor procedures were enrolled. Patients and control demographic parameters, height, weight and single measurement of serum vitamin D, Vitamin B12, ferritin, calcium, phosphorus, zinc were obtained. An ANN prediction model was developed. RESULTS: The statistical analysis reveals that patients with chronic neck pain have significantly lower serum Vitamin D and Ferritin (p-value <.05). 90% of patients with chronic neck pain were females. Multilayer Feed Forward Neural Network with Back Propagation(MFFNN) prediction model were developed and designed based on vitamin D and ferritin as input variables and CNP as output. The ANN model output results show that, 92 out of 108 samples were correctly classified with 85% classification accuracy. CONCLUSIONS: Although Iron and vitamin D deficiency cannot be isolated as the sole risk factors of chronic neck pain, they should be considered as two modifiable risk. The high prevalence of chronic neck pain, hypovitaminosis D and low ferritin amongst women is of concern. Bioinformatics predictions with artificial neural network can be of future benefit in classification and prediction models for chronic neck pain. We hope this initial work will encourage a future larger cohort study addressing vitamin D and iron correction as modifiable factors and the application of artificial intelligence models in clinical practice.

Different DHEA-S Levels and Response Patterns in Individuals with Chronic Neck Pain, Compared with a Pain Free Group-a Pilot Study.

Objective: To test, in this pilot study, whether DHEA-S (Dehydroepiandrosterone, sulfated form) plasma levels are lower among persons with chronic neck pain, compared to control persons, and to investigate the DHEA-S response after a physical exercise. Subjects: Included were 12 persons with chronic neck pain and eight controls without present pain, all 18 and 65 years of age. Exclusion criteria for both groups were articular diseases or tendinosis, fibromyalgia, systemic inflammatory and neuromuscular diseases, pain conditions due to trauma, or severe psychiatric diseases. Design and methods: The participants arm-cycled on an ergometer for 30 minutes. Blood samples were taken before, 60 minutes, and 150 minutes after this standardized physical exercise. Results: The estimated plasma DHEA-S levels at baseline were 2.0 µmol/L (95% confidence interval [CI] 1.00; 4.01) in the pain group and 4.1 µmol/L (95% CI2.0; 8.6) in the control group, adjusted for sex, age, body mass index (BMI), and Shirom-Melamed Burnout Questionnaire (SMBQ), with a ratio of 0.48 ( P = 0.094). Conclusions: In this pilot study, the plasma DHEA-S levels appeared to be lower among the persons with chronic neck pain, compared with the control group. It was indicated that DHEA-S decreased during the physical exercise in the control group, and either increased or was unaffected in the chronic pain group.

Association between plasma concentrations of linoleic acid-derived oxylipins and the perceived pain scores in an exploratory study in women with chronic neck pain.

BACKGROUND: Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and anti-nociceptive compounds, and such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women. METHODS: Blood samples from 35 women with NP, 15 with CWP and 27 age-matched controls were analysed for the lipids using ultra performance liquid chromatography coupled to tandem mass spectrometry. Current pain ("NRSday") and the average pain during the last week ("NRSweek") were rated by the participants using a numerical rating scale. RESULTS: There were no significant differences in the plasma concentrations of the fifteen lipids investigated between the women with pain and the controls. However, significant correlations were seen for the NP group between the NRSday scores and the plasma concentrations of the linoleic acid derivatives 9- and 13-hydroxy-octadecadienoic acid (Spearman's rho values 0.51 [P = 0.0016]) and 0.53 [P = 0.0011], respectively). CONCLUSIONS: The data obtained in this exploratory study indicate that although no group differences are seen in plasma lipid concentrations, there is an association between the NRSday scores and the 9- and 13-hydroxy-octadecadienoic acid levels. Whether or not the association reflects a causality (i.e. that the circulating lipids contribute to the perceived pain of the pain participants), requires further investigation.

The effects of black soybean (Glycine max var.) on chronic cervical pain of sedentary office workers in a northern Chinese population.

Chronic cervical pain is a common symptom of sedentary office workers. Black soybean (Glycine max var.) has rich necessary nutrients for the therapy of chronic pain. Thus, it may ease chronic cervical pain. To prove our claim, 260 sedentary office workers with chronic pain were recruited and they consumed the defined diets at breakfast, lunch, and dinner with 1 g, 5 g and 10 g (3 g, 15 g, 30 g daily) cooked black soybean for 24 weeks. Visual analog scale (VAS), neck disability index (NDI) pain scores and short-form 36 (SF-36) health survey questionnaires were applied in the study. The levels of N-methyl-D-aspartate receptors (NMDAR) were measured. The VAS and NDI pain scores reduced and SF-36 scores increased in a 15 or 30 g black soybean daily group compared with a 3 g black soybean daily group after a 24-week therapy (P < 0.05). The 30 g black soybean daily group was better than the 15 g black soybean daily group in relieving chronic cervical pain of sedentary office workers (p < 0.05). The levels of NMDAR were lower in the 15 or 30 black soybean daily group than those in the 3 g black soybean daily group (P < 0.05). Black soybean can ameliorate chronic cervical pain by down-regulating the levels of NMDAR.

Intramuscular pain modulatory substances before and after exercise in women with chronic neck pain.

BACKGROUND: In peripheral tissue, several substances influence pain and pain modulation. Exercise has been found to decrease pain and improve function for chronic pain conditions, but how and why exercise produces beneficial effects remains unclear. This study investigates whether aspects of pain and concentrations of substances with algesic, analgesic and metabolic functions differ between women with chronic neck shoulder pain (CNSP) and healthy women (CON) and whether changes are found after an exercise intervention for CNSP. METHODS: Forty-one women with CNSP and 24 CON subjects were included. The participants attended two microdialysis sessions with 4-6 months between the experiments. During this period, the CNSP subjects underwent an exercise intervention. Expression levels of substance P, beta-endorphin, cortisol, glutamate, lactate and pyruvate as well as pain intensity and pressure pain thresholds were analysed. RESULTS: At baseline, higher concentrations of glutamate and beta-endorphin and lower concentrations of cortisol in CNSP than CON were found. After exercise, decreased levels of substance P and possibly of glutamate, increased levels of beta-endorphin and cortisol as well as decreased pain intensity and increased pain pressure thresholds were found for CNSP. CONCLUSIONS: The findings at baseline indicated algesic and analgesic alterations in the painful trapezius muscles. The findings for CNSP after the exercise intervention, with changes in peripheral substances and decreased pain intensity and sensitivity, could reflect a long-term physiological effect of the exercise.

Peripheral oxidative stress blood markers in patients with chronic back or neck pain treated with high-velocity, low-amplitude manipulation.

OBJECTIVE: The purpose of this study was to investigate oxidative-stress parameters in individuals with chronic neck or back pain after 5 weeks of treatment with high-velocity, low-amplitude (HVLA) spinal manipulation. METHODS: Twenty-three individuals aged 38.2 ± 11.7 years with nonspecific chronic neck or back pain verified by the Brazilian Portuguese version of the Chronic Pain Grade, with a sedentary lifestyle, no comorbidities, and not in adjuvant therapy, underwent treatment with HVLA chiropractic manipulation twice weekly for 5 weeks. Therapeutic procedures were carried out by an experienced chiropractor. Blood samples were assessed before and after treatment to determine the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), and the levels of nitric oxide metabolites and lipid hydroperoxides. These blood markers were analyzed by paired Student t test. Differences were considered statistically significant, when P was <.05. RESULTS: There was no change in catalase but an increase in SOD (0.35 ± 0.03 U SOD per milligram of protein vs 0.44 ± 0.04 U SOD per milligram of protein; P < .05) and GPx (7.91 ± 0.61 nmol/min per milligram of protein vs 14.07 ± 1.07 nmol/min per milligram of protein; P < .001) activities after the treatment. The nitric oxide metabolites and the lipid hydroperoxides did not change after treatment. CONCLUSION: High-velocity, low-amplitude spinal manipulation twice weekly for 5 weeks increases the SOD and GPx activities. Previous studies have shown a relationship between pain and oxidative and nitrosative parameters; thus, it is possible that changes in these enzymes might be related to the analgesic effect of HVLA spinal manipulation.

Inflammatory biomarkers in serum in subjects with and without work related neck/shoulder complaints.

BACKGROUND: Although it has recently been recognised that inflammation is important in the development of work-related musculoskeletal disorders (MSDs), the exact pathophysiological pathways are unknown. METHODS: We investigated serum concentrations of inflammatory cytokines in 35 female supermarket cashiers with repetitive work tasks and work related neck/shoulder complaints, compared with those from 25 women without MSDs (6 supermarket cashiers and 19 middle-school teachers or faculty staff). None of the subjects were pregnant or lactating, and showed no signs of rheumatoid arthritis, systemic lupus erythematosus, cancer, diabetes, coronary artery disease or inadequately controlled hypertension. Serum levels of IL-1α, IL-1ß, IL-6, IL-8, IL-10, IL-12, MCP-1, MIP-1α, MIP-1ß, TNF-α, GM-CSF, CTGF and CRP were analysed. RESULTS: The women with pain related to MSD had higher serum concentrations of MIP-1ß (median, 25th-75th percentile: 90.0 pg/mL, 62.5-110 vs. 73.1 pg/mL, 54.6-88.3; p = 0.018), IL-12 (0.26 pg/mL, 0.26-0.26 vs. 0.26 pg/mL, 0.26-0.26; p = 0.047) and CRP (0.5 mg/L, 0.5-1.6 vs. 0.5 mg/L, 0.5-0.5; p = 0.003), than control subjects. Levels of MIP-1α, MIP-1ß and CRP were correlated with the reported intensity of neck/shoulder pain (r = 0.29, p = 0.03 for MIP-1α; r = 0.29, p = 0.02 for MIP-1ß and r = 0.43, p = 0.001 for CRP). No statistically significant differences in serum levels were found for the remaining cytokines. CONCLUSIONS: Otherwise healthy females with ongoing work-related neck/shoulder pain showed higher serum concentrations of MIP-1ß, IL-12 and CRP than controls, and the levels of MIP-1α, MIP-1ß and CRP were correlated to pain intensity. These results support previous findings that inflammatory processes play a part in work related MSDs.

Changes in biochemical markers of pain perception and stress response after spinal manipulation.

STUDY DESIGN: Controlled, repeated-measures, single-blind randomized study. OBJECTIVES: To determine the effect of cervical or thoracic manipulation on neurotensin, oxytocin, orexin A, and cortisol levels. BACKGROUND: Previous studies have researched the effect of spinal manipulation on pain modulation and/or range of movement. However, there is little knowledge of the biochemical process that supports the antinociceptive effect of spinal manipulation. METHODS: Thirty asymptomatic subjects were randomly divided into 3 groups: cervical manipulation (n = 10), thoracic manipulation (n = 10), and nonmanipulation (control) (n = 10). Blood samples were extracted before, immediately after, and 2 hours after each intervention. Neurotensin, oxytocin, and orexin A were determined in plasma using enzyme-linked immuno assay. Cortisol was measured by microparticulate enzyme immuno assay in serum samples. RESULTS: Immediately after the intervention, significantly higher values of neurotensin (P<.05) and oxytocin (P<.001) levels were observed with both cervical and thoracic manipulation, whereas cortisol concentration was increased only in the cervical manipulation group (P<.05). No changes were detected for orexin A levels. Two hours after the intervention, no significant differences were observed in between-group analysis. CONCLUSION: The mechanical stimulus provided by spinal manipulation triggers an increase in neurotensin, oxytocin, and cortisol blood levels. Data suggest that the initial capability of the tissues to tolerate mechanical deformation affects the capacity of these tissues to produce an induction of neuropeptide expression. J

Effect of high-velocity, low-amplitude treatment on superoxide dismutase and glutathione peroxidase activities in erythrocytes from men with neck pain.

OBJECTIVE: This study investigates the analgesic effect of high-velocity, low-amplitude (HVLA) manipulation and antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes of men with neck pain. METHODS: Twenty-two men with neck pain of mechanical origin who were aged 20 to 50 years, were nonsmokers, had a sedentary lifestyle, had no comorbidities, and were not in adjuvant therapy underwent 6 sessions of HVLA chiropractic manipulation 3 times a week for 2 weeks. Patients were treated by the same chiropractor and under the same conditions. Blood samples were collected before the beginning of the treatment and at the end of the third and last session. Erythrocytes were separated from blood and then processed to determine SOD and GPx activities. The quadruple visual scale and the Neck Disability Index were used to demonstrate the analgesic effect of treatment. The results were analyzed by repeated-measures analysis of variance followed by Bonferroni posttest. Differences were considered significant when P was less than .05. RESULTS: Despite the tendency to reduction in SOD and increase in GPx activities, there was no significant change after the treatment. CONCLUSION: High-velocity, low-amplitude treatment for 6 sessions in men with neck pain did not affect systemic SOD and GPx activities. Despite the absence of significant changes, this study is important because it is the first to investigate the activities of SOD and GPx in patients with neck pain treated with HVLA spinal manipulation.

Effects of high-velocity, low-amplitude manipulation on catalase activity in men with neck pain.

OBJECTIVE: The aim of this study was to identify the influence of high-velocity, low-amplitude (HVLA) manipulation on lipid peroxidation and catalase activity in subjects with neck pain who answered the Neck Disability Index and quadruple visual scale questionnaires. METHODS: Twenty-two men (mean age, 38 years) with neck pain were recruited through radio and newspaper advertisements in the local media. Every patient received 6 sessions of HVLA manipulation, 3 times a week for 2 weeks. Blood samples were drawn from the cubital vein before treatment in the first session and after the third and sixth sessions. The quadruple visual scale was used with the same scheme. The Neck Disability Index questionnaire was applied before the beginning of treatment and after the last session. Catalase activity and lipoperoxidation were measured in erythrocyte samples. RESULTS: Results showed no change in lipid peroxidation. Nevertheless, the catalase activity was increased by HVLA manipulation. The same treatment reduced pain perception and disability in these subjects. CONCLUSION: The present study has shown that catalase activity of the erythrocytes, but not lipoperoxidation, increased after 6 sessions of HVLA manipulation treatment in men with neck pain. The results support the beneficial role of HVLA in the treatment of patients with neck pain.

Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache.

The goal of this study was to explore the relationship between indicators of sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) activity and stress-induced head and shoulder-neck pain in patients with migraine or tension-type headache (TTH). We measured noradrenaline, adrenaline and cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16 TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 30 min of relaxation. Migraine patients had lower noradrenaline levels in blood platelets compared to controls. Pain responses correlated negatively with noradrenaline levels, and pain recovery correlated negatively with the cortisol change in migraineurs. TTH patients maintained cortisol secretion during the cognitive stress as opposed to the normal circadian decrease seen in controls and migraineurs. There may therefore be abnormal activation of the HPA axis in patients with TTH when coping with mental stress, but no association was found between pain and cortisol. A relationship between HPA activity and stress in TTH patients has to our knowledge not been reported before. In migraine, on the other hand, both sympathoneural activation and HPA activation seem to be linked to stress-induced muscle pain and recovery from pain respectively. The present study suggests that migraineurs and TTH patients cope differently with low-grade cognitive stress.

Immediate influence of transcranial electrostimulation on pain and beta-endorphin blood levels: an active placebo-controlled study.

BACKGROUND: Stimulation of the antinociceptive system by noninvasive electrical current from electrodes placed on the head is a renewed method of pain relief. METHODS: We conducted a randomized, double-blind, placebo-controlled study on 20 chronic back pain patients. They were treated with either transcranial electrostimulation (TCES) or an active placebo device. Pain level and serum beta-endorphin levels were measured before and after treatment. RESULTS: beta-Endorphin level increased in seven of the ten patients from the treatment group and did not change in eight of ten patients from control group (P = 0.057 between groups). Pain level decreased in eight treated patients and seven control patients (significant decrease for each group, no significant difference between groups). CONCLUSIONS: Transcranial electrostimulation is a nonpharmacologic method of pain relief accompanied or mediated by beta-endorphin release. The comparable degree of the initial clinical response emphasizes the powerful placebo effect on reported pain not mediated by endorphin release. This preliminary study shows that noninvasive electrical stimulation is a safe treatment with a positive effect on beta-endorphin blood levels.

Management of chronic pain in whiplash injury.

We investigated the response of chronic neck and shoulder pain to decompression of the carpal tunnel in 38 patients with whiplash injury. We also determined the plasma levels of substance P (SP) and calcitonin gene-related peptide (CGRP), which are inflammatory peptides that sensitise nociceptors. Compared with normal control subjects, the mean concentrations of SP (220 v 28 ng/l; p < 0.0001) and CGRP (400 v 85 ng/l; p < 0.0005) were high in patients with chronic shoulder and neck pain before surgery. After operation their levels fell to normal. There was resolution of neurological symptoms with improvement of pain in 90% of patients. Only two of the 30 with chronic neck and shoulder pain who had been treated conservatively showed improvement when followed up at two years. In spite of having neuropathic pain arising from the median nerve, all these patients had normal electromyographic and nerve-conduction studies. Chronic pain in whiplash injury may be caused by 'atypical' carpal tunnel syndrome and responds favourably to surgery which is indicated in patients with neck, shoulder and arm pain but not in those with mild symptoms in the hand. Previously, the presence of persistent neurological symptoms has been accepted as a sign of a poor outcome after a whiplash injury, but our study suggests that it may be possible to treat chronic pain by carpal tunnel decompression.