Articles: hyperalgesia.
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Biological psychiatry · Nov 2018
Positive Allosteric Modulation of Cannabinoid Receptor Type 1 Suppresses Pathological Pain Without Producing Tolerance or Dependence.
Activation of cannabinoid CB1 receptors suppresses pathological pain but also produces unwanted central side effects. We hypothesized that a positive allosteric modulator of CB1 signaling would suppress inflammatory and neuropathic pain without producing cannabimimetic effects or physical dependence. We also asked whether a CB1 positive allosteric modulator would synergize with inhibitors of endocannabinoid deactivation and/or an orthosteric cannabinoid agonist. ⋯ Positive allosteric modulation of CB1-receptor signaling shows promise as a safe and effective analgesic strategy that lacks tolerance, dependence, and abuse liability.
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Comparative Study
Effects of topical vs injection treatment of cervical myofascial trigger points on headache symptoms in migraine patients: a retrospective analysis.
In migraine patients with cervical myofascial trigger points whose target areas coincide with migraine sites (M + cTrPs), TrP anesthetic injection reduces migraine symptoms, but the procedure often causes discomfort. This study evaluated if a topical TrP treatment with 3% nimesulide gel has similar efficacy as the injection but produces lesser discomfort with higher acceptability by the patients. ⋯ In migraine patients, topical treatment of cervical TrPs with 5% nimesulide gel proves equally effective as TrP injection with local anesthetics but more acceptable by the patients. This treatment could be effectively associated to standard migraine prophylaxis to improve therapeutic outcomes.
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Opioids remain a mainstay in the treatment of acute and chronic pain, despite numerous and potentially dangerous side effects. There is a great unmet medical need for alternative treatments for patients suffering from pain that do not result in addiction or adverse side effects. Anticonvulsants have been shown to be effective in managing pain, though high systemic levels and subsequent side effects limit their widespread usage. Our goal was to determine if the incorporation of an anticonvulsant, carbamazepine, into a biodegradable microparticle for local sustained perineural release would be an efficacious analgesic following a peripheral injury. ⋯ This formulation reduced systemic exposure to carbamazepine over 1,000-fold relative to traditional analgesic dosing regimens. This 2-component drug delivery system has been specifically engineered to release a controlled amount of carbamazepine over a 14-day period, providing significant pain relief with no toxicological or observable adverse events via behavioral or histochemical analysis.
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The aim of this study was to determine whether upregulated cutaneous expression of α1-adrenoceptors (α1-AR) is a source of pain in patients with complex regional pain syndrome (CRPS). Immunohistochemistry was used to identify α1-AR on nerve fibres and other targets in the affected and contralateral skin of 90 patients, and in skin samples from 38 pain-free controls. The distribution of α1-AR was compared between patients and controls, and among subgroups of patients defined by CRPS duration, limb temperature asymmetry, and diagnostic subtype (CRPS I vs CRPS II). ⋯ Although less clearly associated with the nociceptive effects of phenylephrine, α1-AR expression was greater on dermal nerve fibres in the painful than contralateral limb. Together, these findings are consistent with nociceptive involvement of cutaneous α1-AR in CRPS. This involvement may be greater in acute than chronic CRPS, and in CRPS II than CRPS I.
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The exchange proteins activated by cAMP (Epacs) have been shown to play important roles in producing inflammation-induced nociception. Transient receptor potential vanilloid type 1 (TRPV1) is a major receptor processing thermal and chemosensitive nociceptive information. The role of Epacs in modulating the activity of TRPV1 has yet to be determined. ⋯ In addition, CPT increased the expression of phosphorylated PKCα (pPKCα) and membrane TRPV1 expression in DRG. Studying the colocalization of TRPV1 and pPKCα or pPKCε in DRG slices prepared from CFA-treated rats, we found that pPKCα or pPKCε expressed with TRPV1 in different-sized neurons to exert differential influences on TRPV1 activity. Thus, Epac-PKC signaling is critically important in producing inflammation-induced potentiation of TRPV1 functions.