Articles: hyperalgesia.
-
The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. ⋯ Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.
-
Protease-activated receptor type 2 (PAR2) is known to play an important role in inflammatory, visceral, and cancer-evoked pain based on studies using PAR2 knockout (PAR2(-/-)) mice. We have tested the hypothesis that specific activation of PAR2 is sufficient to induce a chronic pain state through extracellular signal-regulated kinase (ERK) signaling to protein synthesis machinery. We have further tested whether the maintenance of this chronic pain state involves a brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (trkB)/atypical protein kinase C (aPKC) signaling axis. ⋯ Systemic injection of the trkB antagonist ANA-12 similarly inhibited PAR2-mediated mechanical hypersensitivity, grimacing, and hyperalgesic priming. Inhibition of aPKC (intrathecal delivery of ZIP) or trkB (systemic administration of ANA-12) after the resolution of 2-at-induced mechanical hypersensitivity reversed the maintenance of hyperalgesic priming. Hence, PAR2 activation is sufficient to induce neuronal plasticity leading to a chronic pain state, the maintenance of which is dependent on a BDNF/trkB/aPKC signaling axis.
-
Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia. We aimed at investigating the combinatorial effect of cold stimuli and topical L-menthol on cold pain and secondary mechanical hyperalgesia. Analogue to the heat-capsaicin model on skin sensitization, we proposed that cold/menthol enhances or prolong L-menthol-evoked sensitization. ⋯ Skin blood flow increased after L-menthol (P < 0.001) and stayed stable after cold cycles. Repeated application of cold on skin treated by L-menthol facilitated and prolonged L-menthol-induced cold pain and hyperalgesia. This model may prove beneficial for testing analgesic compounds when a sufficient duration of time is needed to see drug effects on CPT or mechanical hypersensitivity.
-
The locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a well-established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC. ⋯ GDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.