Pain
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We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. ⋯ Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain.
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The ability to sense and respond to thermal stimuli at varied environmental temperatures is essential for survival in seasonal areas. In this study, we show that mice respond similarly to ramping changes in temperature from a wide range of baseline temperatures. ⋯ The adjustment of this set point requires transient receptor potential cation channel, subfamily member 8 (TRPM8), but not transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and is regulated by phospholipase C (PLC) activity. Overall, our findings suggest that temperature response thresholds in mice are dynamic, and that this ability to adapt to environmental temperature seems to mirror the in vitro findings that PLC-mediated hydrolysis of phosphoinositol 4,5-bisphosphate modulates TRPM8 activity and thereby regulates the response thresholds to cold stimuli.
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Randomized Controlled Trial
Peripheral opioid receptor blockade increases postoperative morphine demands - a randomized, double-blind, placebo-controlled trial.
Experimental studies suggest that a large proportion of opioid analgesia can be mediated by peripheral opioid receptors. This trial examined the contribution of such receptors to clinical analgesia induced by intravenous morphine. We hypothesized that the selective blockade of peripheral opioid receptors by methylnaltrexone (MNX) would increase the patients' demand for morphine to achieve satisfactory postoperative pain relief. ⋯ Secondary endpoints were similar in all groups (P>.05). Thus, a significant proportion of analgesia produced by systemically administered morphine is mediated by peripheral opioid receptors. Drugs that selectively activate such receptors should have the potential to produce powerful clinical pain relief.
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Randomized Controlled Trial
A randomized, double-blind, placebo-controlled trial and open-label extension study to evaluate the efficacy and safety of pregabalin in the treatment of neuropathic pain associated with HIV neuropathy.
The objective of these studies was to assess the efficacy and safety of pregabalin in the treatment of human immunodeficiency virus (HIV)-associated neuropathic pain. Patients with HIV-associated distal sensory polyneuropathy (DSP) were randomized to treatment with flexible-dose pregabalin (150-600 mg/day) or placebo for 17 weeks in a single-blind, placebo lead-in, randomized, double-blind, parallel-group, placebo-controlled multinational trial. The primary efficacy outcome was the change in mean pain score on an 11-point numeric rating scale (NRS) from baseline to study endpoint. ⋯ Overall, this trial did not show pregabalin to be more efficacious than placebo in treating HIV-associated DSP. Studies such as these, which fail to support their primary hypotheses, may be important in informing the methodology of future trials, especially when novel approaches to limit variability in the control group are included. ClinicalTrials.gov identifiers: NCT01049217 and NCT01145417.
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Randomized Controlled Trial
tDCS modulates cortical nociceptive processing but has little to no impact on pain perception.
Transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. Several studies suggest clinical efficacy in chronic pain syndromes. However, little is known regarding its effects on cortical pain processing. ⋯ However, contrasting the interaction of stimulation modes (anodal/cathodal) resulted in a significant decrease of activation in the hypothalamus, inferior parietal cortex, inferior parietal lobule, anterior insula, and precentral gyrus, contralateral to the stimulation site after anodal stimulation, which showed the opposite behavior after cathodal stimulation. Pain ratings and heat hyperalgesia showed only a subclinical pain reduction after anodal tDCS. Larger-scale clinical trials using higher tDCS intensities or longer durations are necessary to assess the neurophysiological effect and subsequently the therapeutic potential of tDCS.