Table 1.
Studies about the antinociceptive effects of CB1 and CB2 receptor agonists in different pain models.
| Pain model | Drug treatment and dose | Behavioral readout | Route | Results | Proposed mechanisms of action | Reference |
|---|---|---|---|---|---|---|
| Partial SNL | WIN 55,212-2 0.3–10 mg/kg CP-55,940 0.03–1 mg/kg HU-210 0.001–0.03 mg/kg | Mechanical hyperalgesia Thermal hyperalgesia Tactile allodynia | s.c. or i.t. | They produce complete reversal of mechanical hyperalgesia with catalepsy Only WIN 55,212-2 reversed tactile allodynia and thermal hyperalgesia in this model | Via activation of CB1 receptors in both CNS and in the periphery | Herzberg et al., 1997; Fox et al., 2001; Bridges et al., 2003 |
| SNL or carrageenan model | AZ11713908 0.6–1.2 μmol/kg | Thermal and mechanical hyperalgesia | s.c. | Robust analgesia in both models | Likely via peripheral activation of CB1 receptor | Yu et al., 2010 |
| Mechanical stimulation, formalin or capsaicin models, in mice that lacked CB1 receptor specifically in primary nociceptors | Endocannabinoids (AEA and arachidonic acid) | Thermal and mechanical hyperalgesia | The nociceptor-specific loss of CB1 receptor substantially reduced the analgesia produced by local and systemic but no intrathecal, delivery of cannabinoids | Via CB1 receptors expressed on the peripheral terminals of nociceptors | Agarwal et al., 2007 | |
| SNL, carrageenan, LPS or CIA model | URB937 1 mg/kg URB597 10 mg/kg PF-3845 0.1-10 μg/kg | Thermal and mechanical hyperalgesia, tactile allodynia | i.p. or i.t. | Attenuation of hyperalgesia and partial reduction of allodynia | Suppresses FAAH activity and increases AEA levels | Clapper et al., 2010; Kinsey et al., 2011; Booker et al., 2012 |
| FCA, partial SNL, tail flick, hot plate or incision model of postoperative pain | GW405833 0.3–30 mg/kg | Mechanical hyperalgesia and tactile allodynia | i.p. | Elicits potent and efficacious antihyperalgesic effects in rodent models of neuropathic, incisional and chronic inflammatory pain | Via activation of CB2 receptors | Valenzano et al., 2005 |
| FCA, chronic constriction injury, incision model of postoperative pain or knee joint osteoarthritic pain | A796260 11–35 mg/kg | Thermal and tactile allodynia | i.p. | Analgesic activity in all pain models | Via activation of CB2 receptors | Yao et al., 2008 |
| Partial SNL or carrageenan model | JWH133 50–100 nmol/mouse | Tactile allodynia | i.t., i.p. or local | Reverses partial sciatic nerve ligation-induced mechanical allodynia in mice. | Via activation of central CB2 receptors | Patel et al., 2003; Elmes et al., 2004; Yamamoto et al., 2008; Sagar et al., 2009 |
| SNL, Formalin, Carrageenan, FCA or intradermal capsaicin | AM1241 0.03–6 mg/kg | Tactile and thermal allodynia, mechanical hyperalgesia and nocifensive response | i.v., i.p. or i.pl. | Analgesic effects in all pain models | Via activation of peripheral CB2 receptors | Malan et al., 2001, 2002; Ibrahim et al., 2003; Quartilho et al., 2003; LaBuda et al., 2005; Beltramo et al., 2006; Hillsley et al., 2007; Yao et al., 2008 |
| Formalin model or postoperative pain | HU308 30, 50 mg/kg | Nocifensive response and actile allodynia | i.p. | Reduces blood pressure, blocks defecation, and elicits anti-inflammatory and peripheral analgesic activity | Via activation of CB2 receptors | Hanus et al., 1999; LaBuda et al., 2005 |
| FCA or chronic constriction injury | GW842166X 0.1–0.3, 15 mg/kg | Mechanical hyperalgesia | p.o. | Very potent analgesic in inflammatory and neuropathic pain models | Potent and highly selective full agonist at the CB2 receptor | Clayton et al., 2004; Giblin et al., 2007; Anand et al., 2008 |
| SNL | A836339 1–3 μmol/kg | Tactile allodynia | i.v. | Reduces both spontaneous and von Frey-evoked firing of WDR neurons in neuropathic rats | Via activation of spinal and peripheral CB2 receptors | McGaraughty et al., 2009 |
| Paclitaxel-neuropathic pain | AM1710 0.1–10 mg/kg | Mechanical and thermal allodynia | i.p. | Suppresses allodynia generated by paclitaxel without central side effects | Via activation of CB2 receptors | Rahn et al., 2011; Deng et al., 2015 |
AEA, anandamide; SNP, spinal nerve ligation; FCA, Freud’s complete adjuvant; CIA, collagen-induced arthritis; LPS, lipopolysaccharide; s.c., subcutaneous; i.p, intraperitoneal; i.t., intrathecal; i.v., intravenous; p.o., oral administration; i.pl, intraplantar.