Pain
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The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using (11)C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. ⋯ The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.
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Review Meta Analysis Guideline
Interventional management of neuropathic pain: NeuPSIG recommendations.
After reviewing available evidence the Neuropathic Pain Special Interest Group could only recommend:
- Epidural injections for herpes zoster neuropathic pain.
- Steroid injections for radiculopathy.
- Spinal cord stimulator for failed back surgery syndrome or Complex Regional Pain Syndrome type 1
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Review Meta Analysis Guideline
Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations.
As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. ⋯ The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment's abuse potential.
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Endogenous TRPV1 agonists such as oxidized linoleic acid metabolites (OLAMs) and the enzymes releasing them [eg, cytochrome P450 (CYP)] are up-regulated after inflammation in the rat. However, it is not known whether such agonists are elevated in human inflammatory pain conditions. Because TRPV1 is expressed in human dental pulp nociceptors, we hypothesized that OLAM-CYP machinery is active in this tissue type and is increased under painful inflammatory conditions such as irreversible pulpitis (IP). ⋯ These data suggest that LA metabolites produced in human inflamed tissues act as TRPV1 agonists and that the metabolite production can be targeted by CYP inhibition. In addition, immunohistochemical analysis of 2 CYP isoforms, CYP2J and CYP3A1, were shown to be predominately expressed in immune cells infiltrating the inflamed dental pulp, emphasizing the paracrine role of CYP enzymes in OLAM regulation. Collectively, our data indicate that the machinery responsible for OLAM production is up-regulated during inflammation and can be targeted to develop potential analgesics for inflammatory-induced dental pain.
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Nerve growth factor (NGF) is involved in the long-term sensitization of nociceptive processing linked to chronic pain. Functional and structural ("sprouting") changes can contribute. Thus, humans report long-lasting hyperalgesia to mechanical and electrical stimulation after intradermal NGF injection and NGF-induced sprouting has been reported to underlie cancer bone pain and visceral pain. ⋯ At the structural level, however, IENF density was not increased by NGF. In conclusion, intradermal NGF induces long-lasting axonal and mechanical sensitization in porcine C nociceptors that corresponds to hyperalgesia observed in humans. Sensitization is not accompanied by increased IENF density, suggesting that NGF-induced hyperalgesia might not depend on changes in nerve fiber density but could be linked to the recruitment of previously silent nociceptors.