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Dorsal root ganglion field stimulation is an analgesic neuromodulation approach in use clinically, but its mechanism is unknown as there is no validated animal model for this purpose. The authors hypothesized that ganglion stimulation is effective in reducing pain-like behaviors in preclinical chronic pain models.
To assess the expression of inflammatory cytokines in the affected and normal skin of postherpetic neuralgia (PHN) patients.
Cognitive impairment is one of the most common complications associated with chronic pain. Almost 20% of chronic pain patients suffer from cognitive impairment, which may substantially influence their quality of life. Levels of major excitatory neurotransmitters in the central nervous system and alterations in the glutamatergic system may influence cognitive function and the pain sensory pathway. In this study, we adopted the spared nerve injury model to establish the progress of chronic pain and investigated the mechanism underlying the cognitive aspect related to it. At behavioral level, using the novel-object recognition test, mechanical hypersensitivity was observed in peripheral nerve-injured rats because they exhibited recognition deficits. We showed a dramatic decrease in hippocampal glutamate concentration using nuclear magnetic resonance and reduced glutamatergic synaptic transmission using whole-cell recordings. These were associated with deficient hippocampal long-term potentiation induced by high-frequency stimulation of the Schaffer collateral afferent. Ultra-high-performance liquid chromatography revealed lower levels of D-serine in the hippocampus of the spared nerve injury rats and that D-serine treatment could restore synaptic plasticity and cognitive dysfunction. The reduction of excitatory synapses was also increased by administering D-serine. These findings suggest that chronic pain has a critical effect on synaptic plasticity linked to cognitive function and may built up a new target for the development of cognitive impairment under chronic pain conditions.
Depressive symptoms are common among individuals with chronic pain. Previous work suggests that chronic pain patients have difficulty regulating emotional responses, which is a risk factor for the development of major depressive disorder (MDD). Function of the mesocorticolimbic system, a neural network associated with reward processing, contributes to emotion regulation. This network's dysfunction has been described in chronic pain and MDD research and potentially underlies the relationship among emotion dysregulation, chronic pain, and MDD development. Given that mood induction paradigms have been used to measure emotion regulation, the present study examined intrinsic mesocorticolimbic functional connectivity (FC) after induced sad mood in individuals with and without chronic low back pain (cLBP). Thirty-three MDD-free individuals (17 cLBP) underwent resting-state scanning before and after sad memory-evoked mood induction. A Group [cLBP, healthy control (HC)] x Mood (Neutral, Sadness) repeated measures ANCOVA was conducted on seed-based FC data using a mesolimbic a priori region of interest. Interaction effects were identified in the orbital frontal cortex and inferior frontal gyrus [F = 21.07, p < .05. h = .5]. Whereas cLBP showed significantly greater FC between these two regions and the mesolimbic seed under neutral mood, FC among these regions increased in HC and decreased in cLBP under sad mood. Exploratory graph theory analyses further describe between-group differences in mesocorticolimbic network properties. Findings support previous literature describing mesocorticolimbic dysfunction in cLBP and demonstrate aberrant function in emotion regulation. Mesocorticolimbic dysfunction during emotion regulation might contribute to the development of certain depressive phenotypes in chronic pain patients.
With the advancement of technology, peripheral nerve stimulation (PNS) has been increasingly used to treat various chronic pain conditions. Its origin is based on the gate control theory postulated by Wall and Melzack in 1965. However, the exact mechanism behind PNS' analgesic effect is largely unknown. In this article, we performed a comprehensive literature review to overview the PNS mechanism of action.
Physical disuse could lead to a state of chronic pain typified by complex regional pain syndrome type I due to fear of pain through movement (kinesiophobia) or inappropriate resting procedures. However, the mechanisms by which physical disuse is associated with acute/chronic pain and other pathological signs remain unresolved. We have previously reported that inflammatory signs, contractures, disuse muscle atrophy, spontaneous pain-like behaviors, and chronic widespread mechanical hyperalgesia based on central plasticity occurred after 2 weeks of cast immobilization in chronic post-cast pain (CPCP) rat model. In this study, we also demonstrated dystrophy-like changes, both peripheral nociceptive signals and activation of the central pain pathway in CPCP rats. This was done by the following methods: (1) vascular permeability (Evans blue dye) and inflammatory- and oxidative stress-related messenger RNA changes (real-time quantitative polymerase chain reaction); (2) immunofluorescence of pERK and/or c-Fos expression in the spino-parabrachio-amygdaloid pathway; and (3) blockade of nociceptive-related signals using sciatic nerve block. Furthermore, we demonstrated tactile allodynia using an optogenetic method in a transgenic rat line (W-TChR2V4), cold allodynia using the acetone test, and activation of dorsal horn neurons in the chronic phase associated with chronic mechanical hyperalgesia using c-Fos immunofluorescence. In addition, we showed that nociceptive signals in the acute phase are involved in chronic pathological pain-like behaviors by studying the effects of sciatic nerve block. Thus, we conclude that physical disuse contributes to dystrophy-like changes, spontaneous pain-like behavior, and chronic widespread pathological pain-like behaviors in CPCP rats after 2 weeks of cast immobilization.
Pain rehabilitation programs are recommended interventions for patients with chronic pain. Average effect sizes are moderate. Physiatrists, based on clinical experience, argue that the present outcome measures underestimate the outcome of pain rehabilitation programs.
To conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain.
Heat shock protein 90 (Hsp90) is a ubiquitous signal transduction regulator, and Hsp90 inhibitors are in clinical development as cancer therapeutics. However, there have been very few studies on the impact of Hsp90 inhibitors on pain or analgesia, a serious concern for cancer patients. We previously found that Hsp90 inhibitors injected into the brain block opioid-induced antinociception in tail flick, paw incision, and HIV neuropathy pain. This study extended from that initial work to test the cancer-related clinical impact of Hsp90 inhibitors on opioid antinociception in cancer-induced bone pain in female BALB/c mice and chemotherapy-induced peripheral neuropathy in male and female CD-1 mice. Mice were treated with Hsp90 inhibitors (17-AAG, KU-32) by the intracerebroventricular, intrathecal, or intraperitoneal routes, and after 24 hours, pain behaviors were evaluated after analgesic drug treatment. Heat shock protein 90 inhibition in the brain or systemically completely blocked morphine and oxymorphone antinociception in chemotherapy-induced peripheral neuropathy; this effect was partly mediated by decreased ERK and JNK MAPK activation and by increased protein translation, was not altered by chronic treatment, and Hsp90 inhibition had no effect on gabapentin antinociception. We also found that the Hsp90 isoform Hsp90α and the cochaperone Cdc37 were responsible for the observed changes in opioid antinociception. By contrast, Hsp90 inhibition in the spinal cord or systemically partially reduced opioid antinociception in cancer-induced bone pain. These results demonstrate that Hsp90 inhibitors block opioid antinociception in cancer-related pain, suggesting that Hsp90 inhibitors for cancer therapy could decrease opioid treatment efficacy.
Exposure to stress is associated with poor outcomes in people with chronic pain. Dispositional variables, such as pain catastrophizing and distress intolerance, may impact reactivity to stressors. Importantly, these variables can be modified with treatment. The aim of this study was to investigate whether pain catastrophizing and distress intolerance were associated with tolerance of a pain stressor or a psychosocial stressor, and heightened negative affect following these stressors. A sample of 50 adults with chronic pain completed self-report measures and pain and psychosocial stress inductions. Results indicated that pain catastrophizing was associated with heightened anxiety during pain induction. Distress intolerance was associated with negative affect following a psychosocial stressor, and with poorer tolerance of the psychosocial stressor. Pain catastrophizing and distress intolerance are related factors, however, they exhibit distinct associations with amplification of pain and psychosocial stress reactivity. These variables may be important treatment targets in people with chronic pain.