The Pain Course: exploring predictors of clinical response to an Internet-delivered pain management program.

There is significant interest in the potential of Internet-delivered pain management programs for adults with chronic pain. Understanding the characteristics of people who do and do not benefit from Internet-delivered programs will help to guide their safe and effective use. Using a large sample from a previous randomised controlled trial of an established Internet-delivered pain management program, the Pain Course, this study (n = 463) examined whether several demographic, clinical, psychological, and treatment-related variables could be used to predict clinical response in levels of disability, depression, anxiety, or average pain. Multiple univariate and multivariate stepwise logistic regressions were used to identify unique predictors of clinical improvement, which, consistent with recommendations, was defined as a ≥30% reduction in symptoms or difficulties from baseline. Several unique predictors of clinical improvement were found. However, no particularly decisive or dominant predictors emerged that were common across time points or across the outcome domains. Reflecting this, the identified predictors explained only 18.1%, 13.7%, 7.6%, and 9.5% of the variance in the likelihood of making a clinical improvement in disability, depression, anxiety, and average pain levels, respectively. The current findings suggest that a broad range of patients may benefit from emerging Internet-delivered pain management programs and that it may not be possible to predict who will or will not benefit on the basis of patients' demographic, clinical, and psychological characteristics.

Monolithic column-based reversed-phase liquid chromatography separation for amino acid assay in microdialysates and cerebral spinal fluid.

The development of a HPLC method using a monolithic C18 column is described using fluorescence detection for the assay of 21 amino acids and related substances with derivatisation using ortho-phthaldialdehyde (OPA) in the presence of 3-mercaptopropionic acid (3-MPA). The method employs a tertiary gradient and has a run time of 24 min. Linearity (r2) for each amino acid was found to be greater than 0.99 up to a 10 microM concentration; reproducibility across all analyses (relative standard deviation (R.S.D.)) was between 0.97 and 6.7% and limit of detection (LOD) between 30 and 300 fmol on column. This method has been applied to the analysis of amino acids in both spinal microdialysis and cerebral spinal fluid samples.

Selective serotonin re-uptake inhibition attenuates evoked glutamate release in the dorsal horn of the anaesthetised rat in vivo.

Augmentation of serotonergic neurotransmission at the level of the dorsal spinal cord is proposed to contribute to the analgesic activity of selective serotonin (5-HT) reuptake inhibitors (SSRIs). In this study we have utilised microdialysis perfusion to determine the effect of two structurally unrelated SSRIs on depolarisation-induced aspartate and glutamate release in the dorsal spinal cord of the anaesthetised rat. Perfusion with artificial extracellular fluid containing 45 mM potassium produced a significant increase in aspartate and glutamate efflux. Sensitivity, at least in part, to antagonism of calcium entry by high extracellular Mg2+ indicated a neuronal origin for a proportion of stimulated release. Reverse dialysis of paroxetine (1-30 microM) reduced the increase in glutamate in a concentration dependent manner, with a significant reduction evident following inclusion in the perfusate of 30 microM. Administration of an equi-potent dose of citalopram (300 micoM) also reduced depolarisation induced glutamate release. Aspartate levels tended to decrease in the presence of paroxetine and citalopram, but this trend did not reach significance. Co-perfusion of paroxetine (30 microM) with the selective 5-HT(1A) receptor antagonist WAY 100635 (100 microM) did not prevent the reduction in depolarisation induced glutamate efflux. These results demonstrate that local administration of SSRIs has an inhibitory influence on evoked release of glutamate in the dorsal horn. This could indicate regulation of excitatory neurotransmission mediated through augmented serotonergic neurotransmission and activation of a serotonergic receptor other than the 1A subtype. Alternatively, direct inhibition with voltage dependent calcium channels, potentially a property intrinsic to molecules with high selectivity for the 5-HT transporter, may underlie this effect.