Chronic pain following whiplash injury and non-specific arm pain (NSAP, previously termed diffuse repetitive strain injury) present clinicians with problems of diagnosis and management. In both patient groups there are clinical signs of altered nerve movement and increased nerve trunk mechanosensitivity. Previous studies of NSAP patients have identified altered median nerve movement at the wrist. The present study uses high frequency ultrasound imaging to examine changes to median nerve movement and clinical examination to assess altered mechanosensitivity of the median nerve. Longitudinal median nerve movement was measured in the forearm during maximal inspiration in nine post-whiplash patients with chronic neck and arm pain and eight controls subjects. Eight NSAP patients and seven controls were also studied. Transverse median nerve movement at the proximal carpal tunnel during 30 degrees wrist extension to 30 degrees flexion was also measured. A clinical examination of nerve trunk allodynia was performed in all subjects. Longitudinal nerve movement in the forearm was reduced by 71% in the post-whiplash patients and by 68% in NSAP patients compared to controls. In the whiplash patients the pattern of transverse median nerve movement at the proximal carpal tunnel was significantly different to controls (patient mean=2.57+/-0.80 mm (SEM) in a radial direction; control mean=0.39+/-0.52 mm in an ulnar direction). Signs of neural mechanosensitivity (i.e. painful responses to median nerve trunk and brachial plexus pressure and stretch) were apparent in both patients groups. Change in nerve tension and neural mechanosensitivity may contribute to symptoms in whiplash and NSAP patients.

Patients with non-specific limb pain often show signs of nerve mechanosensitivity, i.e. local tenderness over nerve trunks and pain in response to limb movements that cause nerve stretch. In such patients a nerve lesion is not apparent, and it has been suggested that local neural inflammation may be a key factor. The present study examines the extent to which nerve fibres in regions of local inflammation respond to small stretches, and whether functional changes occur throughout the primary afferent neurone. A local neuritis was induced in adult rats by wrapping oxidised cellulose saturated in complete Freund's adjuvant (CFA) around the peroneal or sciatic nerves. A small cut was made in the perineurium of some of the peroneal lesioned animals. A- and C-fibre recordings were made 2-10 days post-surgery from filaments dissected proximal to the lesion. Local mechanosensitivity was assessed using a glass probe and by small stretches. Responses to stretch and local pressure were recorded in 7% of C- and 8% of A-fibres from the peroneal nerve following CFA treatment with the sheath opened. A smaller proportion of stretch sensitive fibres were seen in sciatic and peroneal nerves after CFA treatment alone (2% of C- and 3% of A-fibres), but such fibres were not seen in control preparations. The most responsive fibres fired to 3% stretch, which is within the range of nerve stretch seen during normal limb movements. Less than 1% of stretch sensitive fibres had peripheral fields, indicating that most had probably degenerated distally.

Aims/hypothesis: The association of insulin detemir with non-esterified fatty acid binding sites on albumin may limit its transfer from the circulation into the extravascular extracellular space in adipose tissue and muscle, due to the capillary endothelial cell barrier. In the liver, the open sinusoids may expose hepatocytes to insulin detemir, enabling it to have a greater effect in the liver than in peripheral tissues. Methods: We investigated the effects of equipotent doses of insulin detemir and NPH insulin on hepatic glucose rate of appearance (R-a), peripheral glucose rate of disposal (R-d) and glycerol R-a (a measure of lipolysis) using stable isotope techniques. We also investigated the effects of these insulins on NEFA concentrations in seven healthy volunteers during a 16-h euglycaemic clamp. A higher dose of insulin detemir was also studied. Results: There was no difference in the glucose infusion profile between insulin detemir and NPH. Insulin detemir had a greater effect on mean suppression of glucose R-a (mean difference 0.24 mg kg(-1) min(-1); CI 0.09-0.39; p < 0.01), and minimum glucose R-a, with minimum low dose detemir -0.10 +/- 0.15 mg.kg(-1).min(-1) and minimum NPH 0.17 +/- 0.10 mg.kg(-1).min(-1) (p < 0.02). However, it had a lesser effect on mean suppression of NEFA concentrations (mean difference -0.10 mmol/l; CI -0.03 to -0.17; ANOVA, p < 0.02) than NPH. The effect of insulin detemir on glucose R-d and glycerol R-a was not different from NPH. Following high-dose detemir, total glucose infused and maximum glucose R-d were higher (p < 0.02, p < 0.03) and plasma NEFA concentrations lower (p < 0.01) than with low-dose determir. Conclusions/interpretation: This study suggests that insulin detemir, when compared to NPH insulin, has a greater effect on the liver than on peripheral tissues and thus has the potential to restore the physiological insulin gradient.