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Recent technological advances claim to allow quantitative measurement of the functional integrity of both large and small diameter sensory nerve fibers using the current perception threshold (CPT) sensory testing device. This device has yet to be validated against the corresponding gold standard references for sensory testing (thermal sensory testing [TST]) and von Frey tactile hair stimulation [VF]) to correlate its evaluation of similar sensory nerve perceptions. A baseline neurosensory examination using the CPT, TST and VF methods was performed on 19 healthy volunteers. Using a randomized, double-blind, placebo-controlled design, each subject received an alfentanil or diphenhydramine (as a placebo control) infusion in separate study sessions. The order of the study sessions was randomized and separated by 1 week. The 3 neurosensory examinations were repeated at 3 different targeted plasma levels of study drug. Changes in neurosensory thresholds were then compared between the 3 methods. All CPT measurements and the cold pain measurement showed a significantly higher degree of variability than the other TST and VF measurements. There appeared to be a correlation between the CPT 5 Hz pain threshold and the TST cold pain and warm sensation; intravenous alfentanil significantly elevated all 3 detection thresholds. In addition, there was no effect of alfentanil on the VF or the CPT 2000 Hz thresholds. However, we did not see the predicted relation between the 250 Hz CPT stimulus and cool sensation. From these studies, there is some evidence that similar fiber tracts may be measured between the CPT, TST, and VF methods, especially with the CPT 5 Hz measures and C-fiber tract activity.

The objective was to examine the effect of methadone on CD4+ lymphocyte counts and viral load and to expect to document the safety of methadone maintenance in patients with human immune deficiency syndrome. This is a retrospective chart analysis comparing the trends in CD4+ count and viral load in two populations of 21 human immunodeficiency virus (HIV) infected patients, one on methadone maintenance and a methadone non-using group. Each methadone user was matched with a control methadone non-user that had a similar CD4+ at the beginning of the study. For the CD4+ count we compared the slope of regression for each couple of patients. In 15 patients we also collected the viral load, which was measured at 4-6 monthly intervals. The mean length of follow-up was 811 days for the methadone group and 797 days in the control group. There was no statistical difference in the treatment received by the two groups of patients during the study. The slope of regression of CD4+ count showed a significantly steeper decline in the methadone-using patients compared with the methadone non-users (r= 0.487; p< 0.05). The evolution of the HIV-1 RNA levels was the same during the follow-up of mean 186 months in a few of the patients in each of the two groups. Long-term methadone use was associated with a significantly faster decrease of CD4+ count in HIV-1 affected patients compared with methadone non-users. HIV-1 RNA data were found in too few patients to enable any conclusions about the development of viral load in the two groups., (Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.)

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.