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Neuropathic pain is driven by abnormal peripheral and central processing, and treatments are insufficiently effective. Antibodies against nerve growth factor (anti-NGF) have been investigated as a potent analgesic treatment for numerous conditions. However, the peripheral and brain effects of anti-NGF in neuropathic pain remain unknown. We examined the effectiveness of anti-NGF in reducing chronic pain by local administration in a rat model of sciatic constriction injury (CCI). NGF and substance P in the dorsal root ganglion (DRG) and spinal cord were evaluated. Neuronal activation was measured using c-Fos in the anterior cingulate cortex and ventrolateral periaqueductal gray. At 14 days after CCI, anti-NGF promoted a significant dose-dependent improvement in mechanical threshold, thermal withdrawal latency, and cold sensitivity, lasting for 5 h. NGF upregulation in the DRG and spinal cord after CCI was decreased by anti-NGF, while substance P was increased only in the DRG, and the treatment reduced it. Anti-NGF induced a significant reduction of neuronal activation in the anterior cingulate cortex, but not in the ventrolateral periaqueductal gray. This study provides the first evidence of the anti-NGF effects on brain activity. Thus, our findings suggest that anti-NGF improves chronic neuropathic pain, acting directly on peripheral sensitization and indirectly on central sensitization.
Learn More >OnabotulinumtoxinA is effective in preventing chronic migraine (CM); however, the benefit of onabotulinumtoxinA in patients with CM with daily headache is unknown because these patients are typically excluded from clinical trials. This subanalysis of the COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without daily headache.
Learn More >To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, including recommended treatments such as oxygen, commonly used medications such as opioids, and emerging medications such as intranasal ketamine. Particular focus is paid to a large subset of respondents 65 years of age or older.
Learn More >This review compares mindfulness-based stress reduction (MBSR) to cognitive-behavioural therapy (CBT) in its ability to improve physical functioning and reduce pain intensity and distress in patients with chronic pain (CP), when evaluated against control conditions.
Learn More >This study was conducted to investigate sex differences in the prevalence and clinical presentation of migraine and probable migraine in a general population-based sample.
Learn More >Deaths due to opioid overdose have tripled in the last decade. Efforts to curb this trend have focused on restricting the prescription opioid supply; however, the near-term effects of such efforts are unknown.
Learn More >Introduction Analgesic drugs are often prescribed to patients with non-specific low back pain (NSLBP). Recommendations for non-invasive pharmacological management of NSLBP from recent clinical practice guidelines were compared with each other and with the best available evidence on drug efficacy. Areas covered Recommendations concerning opioids, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, antidepressants, anticonvulsants and muscle relaxants from national primary care guidelines published within the last 3 years were included in this review. For each pharmacological treatment, the most recent systematic review was included as the best available evidence on drug efficacy and common adverse effects were summarized. Expert opinion Although differences exist between guidelines, publications are universally moving away from pharmacotherapy due to the limited efficacy and the risk of adverse effects. NSAIDs have replaced paracetamol as the first choice analgesics for NSLBP in many guidelines. Opioids are generally considered to be a last resort, but opioid prescriptions have been increasing over recent years. Upcoming guideline updates should explicitly shift their focus from pain to function and from pharmacotherapy to non-pharmacological treatments; patient education is important to make sure NSLBP patients accept these changes. To improve the quality of NSLBP care, the evidence-practice gap should be closed through guideline implementation strategies.
Learn More >It is presently unclear whether extended-release naltrexone hydrochloride treatment induces pain or aggravates existing pain among individuals with opioid use disorders. We assessed changes in pain among individuals receiving treatment with either extended-release naltrexone hydrochloride or buprenorphine-naloxone hydrochloride.
Learn More >Ensembles of principal neurons in the basolateral amygdala (BLA) generate the initial engrams for fear memories, while projections from the BLA to the medial prefrontal cortex (mPFC) are essential for the encoding, transfer and storage of remote fear memories. We tested the effects of chronic pain on remote fear memories in mice. Male mice underwent classic fear conditioning by pairing a single tone (conditional stimulus, CS) with a single electric foot shock (unconditional stimulus, US). Sciatic nerve constriction was used to induce neuropathic pain at various time points before or after the fear conditioning. The mice with sciatic nerve cuffs implanted 48 h after the fear conditioning showed an increased freezing response to CS when compared to mice without cuffs or when compared to mice in which the nerve cuffing was performed 48 h before the fear conditioning. The enhancing effect of pain on consolidated fear memory was further tested and mice in which the nerve cuffing was performed 14 days after the fear conditioning also showed an increased fear response when tested 56 days later. We used immunostaining to detect morphological changes in the BLA that could suggest a mechanism for the observed increase in fear response. We found an increased number of calbindin/parvalbumin positive neurons in the BLA and increased perisomatic density of GAD65 on projection neurons that connect BLA to mPFC in mice with nerve cuffs. Despite the strong increase of c-Fos expression in BLA and mPFC that was induced by fear recall, neither the BLA to mPFC nor the mPFC to BLA projection neurons were activated in mice with nerve cuffs. Furthermore, non-injured mice had an increased fear response when BLA to mPFC projections were inhibited by a chemogenetic method. In conclusion, this study provides evidence that persistent pain has a significant impact on consolidated fear memories. Very likely the underlying mechanism for this phenomenon is increased inhibitory input onto the BLA to mPFC projection neurons, possibly from neurons with induced parvalbumin expression. Conceivably, the increased fear response to consolidated fear memory is a harbinger for the later development of anxiety and depression symptoms associated with chronic pain.
Learn More >There are few prospective studies providing comprehensive assessment of risk factors for acute and persistent pain after breast surgery. This prospective observational study assessed patient-related, perioperative, and genetic risk factors for severe acute pain and persistent pain following breast cancer surgery.
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