Abstract：
Cannabinoids have been proposed as therapeutics for pain mitigation. Therefore, the antihyperalgesic effects of a proprietary cannabis-derived mixture, Non-Euphoric Phytocannabinoid Elixir #14 (NEPE14), were examined in a persistent Complete Freund\'s Adjuvant (CFA)-induced model of inflammatory pain. The acute antinociceptive and operant behavioral effects of NEPE14 were then compared with single cannabinoid preparations of Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-THC, the synthetic cannabinoid (-)-CP 55,940 (CP), and cannabidiol (CBD). The THC isomers and CP were also administered with cannabinoid-type-1 receptor (CB1R) antagonist, AM251, and NEPE14 was administered in combination with THC or CP. To induce inflammation, CFA or saline was administered into the paw of male and female Wistar rats. After injections, mechanical hypersensitivity was assessed with Von Frey filaments, and thermal hyperalgesia with a thermal probe. Nine Sprague Dawley rats were also trained to respond under a fixed-ratio 30 schedule for food reinforcers during a 60-min session. Response rates were recorded during the session and warm-water tail-withdrawal latency post session. In CFA-administered rats, mechanical and thermal paw-withdrawal thresholds significantly decreased compared to vehicle, indicating hyperalgesia. Both i.p. (6.6-20.7 ml/kg) and o.m. (30-300 μL) NEPE14 significantly reduced the mechanical and thermal hyperalgesia. In contrast, neither NEPE14 (3.7-20.7 mL/kg i.p., 100-1000 μL o.m.) nor CBD (10-100 mg/kg) significantly decreased response rates or increased tail-withdrawal latency. Acute Δ9-THC, Δ8-THC (1-5.6 mg/kg), and CP (0.032-0.18 mg/kg) significantly and dose-dependently decreased overall response rate and increased tail-withdrawal latency compared to vehicle. AM251 significantly antagonized the rate-decreasing effects of THC, and CP, as well as the antinociceptive effects of CP. Combinations of NEPE14 with Δ9-THC or CP were not significantly different from these cannabinoids alone. In summary, while NEPE14 significantly reduced CFA-induced hyperalgesia, it was more similar to CBD than Δ9-THC, Δ8-THC, and CP for significantly reducing thermal nociception and disrupting conditioned behavior.
摘要：
已经提出大麻素作为缓解疼痛的治疗剂。因此,专有大麻衍生混合物的抗痛觉过敏作用，非快感植物大麻素Elixir＃14（NEPE14），在持续的完全弗氏佐剂（CFA）诱导的炎性疼痛模型中进行检查。然后将NEPE14的急性镇痛和手术行为效应与Δ9-四氢大麻酚（Δ9-THC）的单一大麻素制剂进行比较，Δ8-THC,合成大麻素(-)-CP55,940(CP)，和大麻二酚（CBD）。THC异构体和CP也与大麻素1型受体（CB1R）拮抗剂一起施用，AM251和NEPE14与THC或CP联合给药。诱发炎症,将CFA或盐水施用到雄性和雌性Wistar大鼠的爪中。注射后,用VonFrey丝评估机械超敏反应，和用热探针的热痛觉过敏。还训练了9只SpragueDawley大鼠，使其在60分钟的时间内以固定比例的30时间表对食物增强剂做出反应。在会议期间记录反应率，并在会议后记录温水撤尾延迟。在服用CFA的大鼠中，与车辆相比，机械和热爪缩回阈值显着降低，表明痛觉过敏。i.p.（6.6-20.7ml/kg）和o.m.（30-300μl）NEPE14均显着降低了机械和热痛觉过敏。相比之下,既没有NEPE14(3.7-20.7ml/kg腹膜内注射，100-1000μlo.m.）或CBD（10-100mg/kg）显着降低了反应率或增加了尾部退缩潜伏期。急性Δ9-THC，Δ8-THC（1-5.6mg/kg），与载体相比，CP（0.032-0.18mg/kg）显着并且剂量依赖性地降低了总体反应率，并增加了尾退缩潜伏期。AM251显著拮抗THC的降速效应，CP,以及CP的镇痛作用。NEPE14与Δ9-THC或CP的组合与这些单独的大麻素没有显著差异。总之,而NEPE14显著降低CFA诱导的痛觉过敏，它比Δ9-THC更类似于CBD，Δ8-THC,和CP用于显着降低热伤害感受和破坏条件行为。
