Articles: hyperalgesia.
-
Clinical Trial
NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin.
Nerve growth factor (NGF) modulates sensitivity and sprouting of nociceptors. We explored the spatial and temporal sensitization induced by NGF injection (1 microg) in human skin. Hyperalgesia was investigated in 16 volunteers (36+/-9 years) at day 1, 3, 7, 21, and 49. ⋯ Spatially restricted hyperalgesia indicates a peripheral rather than central mechanism. The temporal profile of lasting nociceptor sensitization suggests an altered peripheral axonal expression of sensory proteins specifically leading to mechanical and thermal sensitization. Intradermal NGF administration provokes a pattern of sensitization that can be used as experimental model for neuropathic pain.
-
Opioids are invaluable in the treatment of moderate-to-severe pain. Unfortunately, their prolonged use may be associated with the onset of opioid-induced hyperalgesia (OIH). This review focuses on recent clinical studies that support or refute the existence of OIH in patients. ⋯ Improvements in paradoxical pain intensity upon discontinuation of opioid therapy suggests that a multidisciplinary method of pain relief is favoured for chronic-pain patients. Quantitative-sensory testing of pain is offered as the most appropriate way of diagnosing hyperalgesia. We can, thus far only reliably validate the existence of OIH development in normal human volunteers receiving acute-morphine infusions.
-
The aim of this study was to investigate bilateral pressure-pain sensitivity over the trigeminal region, the cervical spine, and the tibialis anterior muscle in patients with mechanical chronic neck pain. Twenty-three patients with neck pain (56% women), aged 20 to 37 years old, and 23 matched controls (aged 20 to 38 years) were included. Pressure pain thresholds (PPTs) were bilaterally assessed over masseter, temporalis, and upper trapezius muscles, the C5-C6 zygapophyseal joint, and the tibialis anterior muscle in a blinded design. The results showed that PPT levels were significantly decreased bilaterally over the masseter, temporalis, and upper trapezius muscles, and also the C5-C6 zygapophyseal joint (P < .001), but not over the tibialis anterior muscle (P = .4) in patients with mechanical chronic neck pain when compared to controls. The magnitude of PPT decreases was greater in the cervical region as compared to the trigeminal region (P < .01). PPTs over the masseter muscles were negatively correlated to both duration of pain symptoms and neck-pain intensity (P < .001). Our findings revealed pressure-pain hyperalgesia in the trigeminal region in patients with mechanical chronic neck pain, suggesting spreading of sensitization to the trigeminal region in this patient population. ⋯ This article reveals the presence of bilateral pressure-pain hypersensitivity in the trigeminal region in patients with idiopathic neck pain, suggesting a sensitization process of the trigemino-cervical nucleus caudalis in this population. This finding has implications for development of management strategies.
-
Most previous studies indicated that patients suffering from major depressive disorder (MDD) showed a decreased sensitivity for external or skin surface pain, eg, for heat or electrical stimuli, as compared to healthy controls. Here, we investigated cold-pain thresholds in 20 unmedicated patients suffering from MDD and 20 matched controls. We applied the ascending method of limits which has previously been used for heat-pain assessment in patients with depression. Similar to previous results for heat-pain thresholds we found a decreased sensitivity for cold pain in patients with MDD as indicated by increased cold-pain thresholds. This difference was significant on the right arm, whereas only a trend was obtained on the left arm, thus suggesting a certain degree of lateralization, similar to that seen in heat-pain perception in patients suffering from MDD or adjustment disorder. The study confirms our previous results of a lower sensitivity for externally induced pain in patients with MDD. Moreover, it adds weight to the assumption of a lateralized perception of thermal pain in depression. ⋯ This investigation provides further evidence for reduced pain perception of externally applied stimuli in major depression. Thus, central-nervous correlates for this altered pain perception in major depression are worth examining in future studies in order to gain more insight into mechanisms of pain perception on the one hand, and pathology of depression on the other.
-
Acid-sensing ion channels (ASICs) respond to acidosis that normally occurs after inflammation. We examined the expression of ASIC1, ASIC2, and ASIC3 mRNAs in lumbar dorsal root ganglion neurons before and 24 hours after carrageenan-induced muscle inflammation. Muscle inflammation causes bilateral increases of ASIC2 and ASIC3 but not ASIC1 (neither ASIC1a nor ASIC1b) mRNA, suggesting differential regulation of ASIC1 versus ASIC2 and ASIC3 mRNA. Similar mRNA increases were observed after inflammation in knockout mice: ASIC2 mRNA increases in ASIC3-/- mice; ASIC2 and ASIC3 mRNAs increase in ASIC1-/- mice. Prior behavioral studies in ASIC3-/- mice showed deficits in secondary hyperalgesia (increased response to noxious stimuli outside the site of injury) but not primary hyperalgesia (increased response to noxious stimuli at the site of injury). In this study, we show that ASIC1-/- mice do not develop primary muscle hyperalgesia but develop secondary paw hyperalgesia. In contrast, and as expected, ASIC3-/- mice develop primary muscle hyperalgesia but do not develop secondary paw hyperalgesia. The pharmacological utility of the nonselective ASIC inhibitor A-317567, given locally, was tested. A-317567 reverses both the primary and the secondary hyperalgesia induced by carrageenan muscle inflammation. Thus, peripherally located ASIC1 and ASIC3 play different roles in the development of hyperalgesia after muscle inflammation. ⋯ This study shows changes in ASIC mRNA expression and behavioral hyperalgesia of C57Bl/6 (wild type), ASIC1-/-, and ASIC3-/- mice before and after the induction of muscle inflammation. A-317567 was effective in reversing hyperalgesia in these animals, suggesting the potential of ASICs as therapeutic targets for muscle inflammatory pain.