HEP (2005) 168:509–554
©cSpringer-Verlag 2005
Cannabinoid Mechanisms of Pain Suppression
J.M. Walker^1 ·A.G.Hohmann^2 ()
(^1) Department of Psychology, Indiana University Bloomington, IN, 47405-7007, USA
(^2) Neuroscience and Behavior Program, Department of Psychology,
The University of Georgia, Athens GA, 30602, USA
[email protected]
1 Brief Overview of Pain Mechanisms ....................... 511
1.1 Nociceptors .................................... 511
1.2 AscendingPainPathways ............................. 512
1.2.1SpinothalamicTract................................ 512
1.2.2DorsalColumnVisceralPainPathway ...................... 512
1.3 DescendingModulationofPain.......................... 513
1.3.1DescendingPainInhibition............................ 513
1.3.2DescendingPainFacilitation ........................... 514
1.4 ImplicationsforUnderstandingCannabinoidActionsinPain ......... 514
2 Antinociception and Suppression of Pain Neurotransmission
by Systemically Administered Cannabinoids .................. 514
3 CB1R-Mediated Antinociception: Peripheral, Spinal, and Supraspinal Actions 516
3.1 MethodologicalConsiderations.......................... 516
3.2 Antinociception Mediated by CB1Rs in the Periphery.. ............ 517
3.2.1 Phenotypes of Dorsal Root Ganglion Cells
Expressing CB1Rs and CB1R mRNA....................... 518
3.2.2AxonalTransportofCBRstothePeriphery ................... 520
3.2.3 Peripheral CB1R-Mediated Antinociception: Acute and Persistent Pain States. 520
3.3 Antinociception Mediated by CB1R in Spinal Cord ............... 523
3.3.1DistributionofCBRsonCentralTerminalsofPrimaryAfferents........ 523
3.3.2 Distribution of CB1R mRNA and CB1R Immunoreactivity in Spinal Cord... 524
3.3.3 Evidence for CB1Rs on Spinal Interneurons ................... 525
3.3.4 Evidence for CB1Rs on Afferents Originating Supraspinally .......... 526
3.3.5 Evidence for CB1Rs on Nonneuronal Cells at the Spinal Level ......... 526
3.3.6 Antinociceptive and Electrophysiological Effects
ofSpinallyAdministeredCannabinoids ..................... 526
3.4 Antinociception Mediated by CB1Rs in Supraspinal Pain Circuits.. ..... 527
3.4.1RoleofthePeriaqueductalGray ......................... 528
3.4.2RoleofRostralVentralMedulla.......................... 529
3.4.3RoleoftheBasolateralAmygdala......................... 529
4 Antinociception Mediated by CB2Rs....................... 530
4.1 Localization of CB2Rs that Contribute to Cannabinoid Antinociception.... 530
4.2 CB2R-Mediated Antinociceptive Effects. .................... 531
5 Pain Modulation by Endocannabinoids ..................... 532
5.1 Anandamide.................................... 533
5.1.1EffectsofExogenousAnandamideonPainSensitivity ............. 533