Articles: hyperalgesia.
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Comparative Study
Reliability of pain threshold measurement in young adults.
The objective was to examine reliability of pressure and thermal (cold) pain threshold assessment in persons less than 25 years of age, using intra-class correlation (ICC) and coefficients of repeatability and variability. We measured thresholds to pain from pressure algometry and ice placed at the hand and head in 10 healthy volunteers aged 18-25. Intra-rater reliability was examined with ICC. ⋯ Reliability of repeat assessments was high as assessed by ICC, although coefficients of repeatability and variation indicated considerable inter-individual variation in repeat measurements. Pressure algometry and strategically placed ice appear to be reliable techniques for assessing pain processing in young adults. Reliability studies employing ICC may benefit from complementary estimation of CR and CV.
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Opioid analgesics are effective for treating many pain conditions. Opioid analgesic tolerance is a pharmacologic phenomenon that could affect the clinical use of opioid analgesics. ⋯ Thus, exposure to opioids could lead to two seemingly unrelated cellular processes (ie, the development of opioid tolerance and opioid-induced pain sensitivity). Their converging effects may be part of the mechanisms leading to the reduced opioid analgesic efficacy in chronic opioid therapy.
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Peripheral nerve injury may lead to neuropathic pain, which is often associated with mechanical and thermal allodynia, ectopic discharge of from injured nerves and from the dorsal root ganglion neurons, and elevated levels of proinflammatory cytokines, particularly interleukin-1 (IL-1). In the present study, we tested the role of IL-1 in neuropathic pain models using two mouse strains impaired in IL-1 signaling: Deletion of the IL-1 receptor type I (IL-1rKO) and transgenic over-expression of the IL-1 receptor antagonist (IL-1raTG). Neuropathy was induced by cutting the L5 spinal nerve on one side, following which mechanical and thermal pain sensitivity was measured. ⋯ WT mice developed progressive autotomy, beginning at 7 days post-injury, whereas the mutant strains displayed delayed onset of autotomy and markedly reduced severity of the autotomy score. Electrophysiological assessment revealed that in WT mice a significant proportion of the dorsal root axons exhibited spontaneous ectopic activity at 1, 3, and 7 days following spinal nerve injury, whereas in IL-1rKO and IL-1raTG mice only a minimal number of axons exhibited such activity. Taken together, these results suggest that IL-1 signaling plays an important role in neuropathic pain and in the altered neuronal activity that underlies its development.
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Chemical and cold sensitivity of two distinct populations of TRPM8-expressing somatosensory neurons.
The cold- and menthol-sensing TRPM8 receptor has been proposed to have both nonnociceptive and nociceptive functions. However, one puzzle is how this single type of receptor may be used by somatosensory neurons to code for two distinct sensory modalities. Using acutely dissociated rat dorsal root ganglion (DRG) neurons without culture, we show that TRPM8 receptors are expressed on two distinct classes of somatosensory neurons. ⋯ Furthermore, low concentrations of menthol produce strong selection of the MS/CIS neuron population over the MS/CS neuron population. On the other hand, the population selection becomes weaker with higher concentrations of menthol. TRPM8 current density shows significant higher in MS/CIS neurons than in MS/CS neurons, suggesting different expression levels of TRPM8 receptors between the two neuron populations, and this difference may provide a mean of selective activation of MS/CIS neurons at low stimulation intensity.
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J. Pharmacol. Exp. Ther. · Feb 2006
High-efficacy 5-hydroxytryptamine 1A receptor activation counteracts opioid hyperallodynia and affective conditioning.
Pain may become intractable as tolerance develops to opioids and the opioids, paradoxically, induce pain. We examined the hypothesis that the analgesia produced by the novel analgesic and high-efficacy 5-hydroxytryptamine (5-HT)(1A) receptor agonist (3-chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]methyl]piperidin-1-yl]methanone, fumaric acid salt (F 13640) may counteract opioid-induced pain. In studies of the somatosensory quality of pain in infraorbital nerve-injured rats, morphine infusion (5 mg/day) by means of osmotic pumps initially caused analgesia (i.e., decreased the behavioral response to von Frey filament stimulation), followed by hyperallodynia and analgesic tolerance. ⋯ The data confirm that opioids produce bidirectional hypo- and proalgesic actions, and offer initial evidence that high-efficacy 5-HT(1A) receptor activation counteracts both the sensory and the affective/motivational qualities of opioid-induced pain. The data also indicate that F 13640 may be effective with opioid-resistant pain. It further is suggested that opioid addiction may represent self-therapy of opioid-induced pathological pain.