Articles: hyperalgesia.
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Opioid-induced hyperalgesia (OIH) and allodynia is a well-known phenomenon and refers to the pain sensitization in patients after prolonged opioid exposure. OIH limits the use of opioids in pain control, but the underlying mechanisms are not fully clear. This study investigated the role of mitochondrial Ca2+ uniporter (MCU) in remifentanil (a commonly used opioid analgesic)-induced allodynia. ⋯ Western blot and immunohistochemistry showed that pNR [phosphorylated N-methyl-D-aspartate (NMDA) receptor] and pERK (phosphorylated extracellular signal-regulated kinase) are increased during both incision-induced hyperalgesia and remifentanil-induced hyperalgesia, and again the increases in pNR and pERK were remarkably attenuated by Ru360. Together, our data demonstrate that MCU plays a critical role in remifentanil-induced postoperative mechanical allodynia, with NMDA receptor and ERK as possible downstream effectors. Our findings provide novel mechanisms for remifentanil-induced mechanical allodynia and encourage future studies to examine the mitochondrial Ca2+ uniporter as a potential therapeutic target for prevention of OIH.
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Amplification of sensory signalling within the nervous system along with psychosocial factors contributes to the variation and severity of knee pain. Quantitative sensory testing (QST) is a non-invasive test battery that assesses sensory perception of thermal, pressure, mechanical and vibration stimuli used in the assessment of pain. Psychosocial factors also have an important role in explaining the occurrence of pain. The aim was to determine whether QST measures were associated with self-reported pain, and whether those associations were mediated by psychosocial factors. ⋯ Associations between mechanical hyperalgesia at the forearm and knee, psychosocial factors and increased levels of clinical global and knee pain intensity provide evidence of altered central processing as a key mechanism in knee pain, with psychological factors playing a key role in the expression of clinical pain.
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To observe the effect of electroacupuncture (EA) on mechanical hyperalgesia threshold (MHTs) and thermal hyperalgesia threshold (THTs) and content of proteinase-activated receptors 2 (PAR 2) in dorsal root ganglia (DRG) in rats with inflammatory pain, so as to explore its peripheral mechanism underlying improvement of inflammatory pain. ⋯ EA can suppress hyperalgesia priming in inflammatory pain rats which may be related to its effect in down-regulating PAR 2 level in the lumbar DRGs.
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Neuroscience letters · Jan 2018
Graded photochemical spinal cord injury results in chronic hyperalgesia and depression-like behaviour but no anxiety exacerbation in female BALB/c mice.
Neuropathic pain (NP) is present in 40-to-50% of spinal cord injured patients. It tends to chronicity and correlates with lower quality-of-life. Moreover, the role of NP in the eventual exacerbation of anxiety- and depression-like behaviours during its development and chronification in genetically susceptible individuals remains unclear. ⋯ Behavioural data suggest that whilst hyperalgesia associated to SCI does not exacerbate BALB/c anxiety-like behaviours, it may result in depression-like behaviour at SCI chronic phase. Our study demonstrates that chronic central hyperalgesia may exacerbate despair-like behaviour at the SCI chronic phase in a mouse model of high anxiety-related behaviour. This implies that photochemical-SCI may be a suitable model to study the comorbidity between chronic NP and mood disorders.
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We studied, in male Sprague Dawley rats, the role of the cognate hyaluronan receptor, CD44 signaling in the antihyperalgesia induced by high molecular weight hyaluronan (HMWH). Low molecular weight hyaluronan (LMWH) acts at both peptidergic and nonpeptidergic nociceptors to induce mechanical hyperalgesia that is prevented by intrathecal oligodeoxynucleotide antisense to CD44 mRNA, which also prevents hyperalgesia induced by a CD44 receptor agonist, A6. Ongoing LMWH and A6 hyperalgesia are reversed by HMWH. ⋯ While low molecular weight HA increases sensitivity to mechanical stimulation, high molecular weight HA reduces sensitization, attenuating inflammatory and neuropathic hyperalgesia. Both pronociceptive and antinociceptive effects of HA are mediated by activation of signaling pathways downstream CD44, the cognate HA receptor, in nociceptors. These results contribute to our understanding of the role of the extracellular matrix in pain, and indicate CD44 as a potential therapeutic target to alleviate inflammatory and neuropathic pain.