Lidocaine is clinically widely used as a local anesthetic inhibiting propagation of action potentials in peripheral nerve fibers. Correspondingly, the functional magnetic resonance imaging (fMRI) response in mouse brain to peripheral noxious input is largely suppressed by local lidocaine administered at doses used in a clinical setting. We observed, however, that local administration of lidocaine at doses 100 lower than that used clinically led to a significantly increased sensitivity of mice to noxious forepaw stimulation as revealed by fMRI. This hyperalgesic response could be confirmed by behavioral readouts using the von Frey filament test. The increased sensitivity was found to involve a type 1...

PnTx4(6-1), henceforth renamed δ-Ctenitoxin-Pn1a (δ-CNTX-Pn1a), a peptide from Phoneutria nigriventer spider venom, initially described as an insect toxin, binds to site 3 of sodium channels in nerve cord synaptosomes and slows down sodium current inactivation in isolated axons in cockroaches (Periplaneta americana). δ-CNTX-Pn1a does not cause any apparent toxicity to mice, when intracerebroventricularly injected (30 µg). In this study, we evaluated the antinociceptive effect of δ-CNTX-Pn1a in three animal pain models and investigated its mechanism of action in acute pain. In the inflammatory pain model, induced by carrageenan, δ-CNTX-Pn1a restored the nociceptive threshold of rats, when intraplantarly injected, 2 h and 30 min after...

Background—Athletes with injury-related pain, especially National Football League (NFL) players, are at increased risk for opioid use and misuse which may result in medical, psychiatric and social problems. This is the first study to evaluate the intersection of sports pain and opioid use and misuse among former NFL players. Methods—A telephone survey of 644 retired NFL players from the 2009 Retired Players Association Directory was conducted (53.4% completion rate) from March to August 2010. Results—Over half (52%) used opioids during their NFL career with 71% reporting misuse. Additionally, 15% of NFL misusers currently misused vs. 5% among players who used just as prescribed during...

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome,...

Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti‐in‐ flammatory and anti‐anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell‐shaped dose‐response was observed, which limits its clinical use. In the present study, we have studied in mice the anti‐inflammatory and anti‐nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between...

AIM Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODS A literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. RESULTS Nonsteroidal anti-inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods...

Abstract Neuropathic pain affects between 5% and 10% of the US population and can be refractory to treatment. Opioids may be recommended as a second-line pharmacotherapy but have risks including overdose and death. Cannabis has been shown to be effective for treating nerve pain without the risk of fatal poisoning. The author suggests that physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. This harm reduction strategy may reduce the morbidity and mortality rates associated with prescription pain medications.

Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were...

Background: Central pain in multiple sclerosis (MS) is common and often refractory to treatment. Methods: We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment. Each spray delivered 2.7 mg of THC and 2.5 of CBD, and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours. Results: Sixty-four patients (97%) completed the trial, 34 received CBM. In week 4, the mean number of daily...