Articles: hyperalgesia.
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Previous reviews have reported that manifestations of pain sensitization may play an important role in the pain experienced by people with knee osteoarthritis. However, it is unknown if manifestations of pain sensitization are common features across other painful knee disorders or if sensitization requires targeted intervention. This review aims to synthesize the published research investigating manifestations of pain sensitization in painful knee disorders and to evaluate if the manifestations of pain sensitization change in response to treatment. ⋯ Our meta-analysis provides evidence of pain sensitization in people with knee osteoarthritis (strong evidence), people with patellofemoral pain (moderate evidence), and postmeniscectomy patients (very limited evidence). However, conflicting evidence exists in patellar tendinopathy. Metaregression indicates that pain is associated with pressure pain thresholds in knee osteoarthritis. In people with knee osteoarthritis and patellofemoral pain, several interventions were found to reduce manifestations of pain sensitization. This review highlights that pain sensitization may be amenable to treatment through exercise therapy, mobilization, and pharmacological and surgical intervention.
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Sickle cell disease (SCD) pain associates with cold temperature and touch. Patients and murine models with SCD have baseline thermal and mechanical pain. In SCD mice, the baseline hypersensitivity is exacerbated by experimental vaso-occlusive crises. ⋯ There were no differences in heat pain sensitivity. The increased cold (P = 0.02) and mechanical (P = 0.0016) pain sensitivity during hospitalization persisted after adjusting for age, sex, hydroxyurea use, opioid consumption, and numeric pain score. Thus, cold and mechanical pain is significantly worse during an acute SCD painful event as compared to baseline health in patients with SCD.
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Spinal cord stimulation (SCS) represents an important neurostimulation therapy for pain. A new ultra-high frequency (10,000 Hz) SCS paradigm has shown improved pain relief without eliciting paresthesia. We aim to determine whether sub-sensory threshold SCS of lower frequencies also can inhibit mechanical hypersensitivity in nerve-injured rats and examine how electric charge delivery of stimulation may affect pain inhibition by different patterns of subthreshold SCS. ⋯ Inhibition of neuropathic mechanical hypersensitivity can be achieved with low-frequency subthreshold SCS by optimizing the electric charge delivery, which may affect the effect of SCS in individual animals.
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Pain sensitivity is characterized by interindividual variability, determined by factors including genetic variation of nociceptive receptors and pathways. The sigma-1 receptor (SIGMAR1) is involved in pain modulation especially under pre-sensitized conditions. However, the contribution of SIGMAR1 genetic variants to pain generation and sensitivity is unknown yet. ⋯ This study indicates lack of association of SIGMAR1 -297G>T and 5A>C genetic variants to susceptibility to develop chronic pain, but significant modulation of somatosensory function in neuropathic pain patients. PERSPECTIVE: This article presents the first study indicating a modulation of somatosensory function in neuropathic pain patients by selected genetic variants in SIGMAR1. As our findings could contribute to the explanation of interindividual differences in drug response they might help to improve the treatment of neuropathic pain.
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We showed previously that spinal metabotropic glutamate receptor 1 (mGluR1) signaling suppresses or facilitates (depending on the stage of estrous cycle) analgesic responsiveness to intrathecal endomorphin 2, a highly mu-opioid receptor-selective endogenous opioid. Spinal endomorphin 2 antinociception is suppressed during diestrus by mGluR1 when it is activated by membrane estrogen receptor alpha (mERα) and is facilitated during proestrus when mGluR1 is activated by glutamate. In the current study, we tested the hypothesis that in female rats subjected to spinal nerve ligation (SNL), the inhibition of spinal estrogen synthesis or blockade of spinal mERα/mGluR1 would be antiallodynic during diestrus, whereas during proestrus, mGluR1 blockade would worsen the mechanical allodynia. ⋯ Findings suggest menstrual cycle stage-specific drug targets for and the putative clinical utility of harnessing endogenous opioids for chronic pain management in women, as well as the value of, if not the necessity for, considering menstrual cycle stage in clinical trials thereof. PERSPECTIVE: Intrathecal treatments that enhance spinal endomorphin 2 analgesic responsiveness under basal conditions lessen mechanical allodynia in a chronic pain model. Findings provide a foundation for developing drugs that harness endogenous opioid antinociception for chronic pain relief, lessening the need for exogenous opioids and thus prescription opioid abuse.