Pain
-
Comparative Study
The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients.
Catechol-O-methyltransferase (COMT) inactivates dopamine, epinephrine and norepinephrine in the nervous system. A common functional polymorphism (Val158Met) leads to a three- to-four-fold variation in the COMT enzyme activity, the Met form displaying lower enzymatic activity. The Val158Met polymorphism affects pain perception, and subjects with the Met/Met genotype have the most pronounced response to experimental pain. ⋯ Patients with the Val/Val genotype (n=44) needed more morphine (155+/-160 mg/24 h) when compared to the Val/Met (117+/-100 mg/24 h; n=96) and the Met/Met genotype (95+/-99 mg/24 h; n=67) groups (P=0.025). This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, perceived pain intensity, adverse symptoms, or time until death. These results suggest that genetic variation in the COMT gene may contribute to variability in the efficacy of morphine in cancer pain treatment.
-
Comparative Study
Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats.
NR1 is an essential component of functional NMDA receptors and can be activated by phosphorylation. It is suggested that phosphorylation of NR1 (pNR1) contributes to central sensitization after intradermal capsaicin injection. The present study investigates whether increases of spinal pNR1 are correlated to central sensitization and thus pain behaviors in neuropathic pain. ⋯ A protein kinase A inhibitor, H89, moderately reversed mechanical allodynia in 7 day neuropathic rats. Many pNR1-immunoreactive neurons were identified as projection neurons by retrograde tracer. The data suggest that PKA mediated NMDA receptor phosphorylation plays an important role in spinal nerve ligation induced neuropathic pain.
-
Comparative Study
Muscle fiber conduction velocity of the upper trapezius muscle during dynamic contraction of the upper limb in patients with chronic neck pain.
The purpose of this study was to compare average muscle fiber conduction velocity (CV) and its changes over time in the upper trapezius muscle during a repetitive upper limb task in people with chronic neck pain and in healthy controls. Surface EMG signals were detected bilaterally from the upper trapezius muscle of 19 patients and nine healthy controls using linear adhesive arrays of four electrodes. Subjects were asked to tap their hands in a cyclic manner between targets positioned mid-thigh and 120 degrees of shoulder flexion, to the beat of a metronome set at 88 beats/min for up to 5 min. ⋯ Furthermore, the exercise-induced decrease in CV over time was enhanced in the patient group (P<0.05). It was concluded that membrane muscle fiber properties of the upper trapezius and their changes over time during dynamic contraction of the upper limb are different in a sample of people with chronic neck pain with respect to controls. This may be associated with the histological and morphological changes, which have previously been identified in people with pain over the trapezius muscle.
-
Comparative Study
Antihyperalgesic properties of the cannabinoid CT-3 in chronic neuropathic and inflammatory pain states in the rat.
CT-3 (ajulemic acid) is a synthetic analogue of a metabolite of Delta9-tetrahydrocannabinol that has reported analgesic efficacy in neuropathic pain states in man. Here we show that CT-3 binds to human cannabinoid receptors in vitro, with high affinity at hCB1 (Ki 6 nM) and hCB2 (Ki 56 nM) receptors. In a functional GTP-gamma-S assay CT-3 was an agonist at both hCB1 and hCB2 receptors (EC50 11 and 13.4 nM, respectively). ⋯ Pharmacokinetic analysis showed that CT-3 exhibits significant but limited brain penetration, with a brain/plasma ratio of 0.4 measured following oral administration, compared to ratios of 1.0-1.9 measured following subcutaneous administration of WIN55,212-2 or Delta9-THC. These data show that CT-3 is a cannabinoid receptor agonist and is efficacious in animal models of chronic pain by activation of the CB1 receptor. Whilst it shows significant cannabinoid-like CNS activity, it exhibits a superior therapeutic index compared to other cannabinoid compounds, which may reflect a relatively reduced CNS penetration.
-
Many reports have shown the efficacy of cannabinoid agonists in chronic pain, whereas no report exists concerning the potential effect of cannabinoid antagonists following prolonged treatment. We tested the effects of repeated administration of the selective cannabinoid receptor type 1 (CB1) antagonist, SR141716 (rimonabant), in rats with chronic constriction injury of the sciatic nerve (CCI), an animal model of neuropathic pain. The repeated oral administration of SR141716 (1, 3 and 10 mg/kg, once a day for 1 week, from day 7 after the injury) dose dependently attenuated both thermal and mechanical hyperalgesia. ⋯ This suggests that the compound may favour myelin repair and consequently promote long-lasting functional recovery. This was confirmed by the maintenance of recovery for at least four weeks after treatment discontinuation. In conclusion, the present findings suggest that SR141716 is effective not only in alleviating neuropathic pain but also in favouring the nerve myelin repair.