PMID- 14581123 OWN - NLM STAT- MEDLINE DCOM- 20040113 LR - 20220408 IS - 0304-3959 (Print) IS - 1872-6623 (Electronic) IS - 0304-3959 (Linking) VI - 106 IP - 1-2 DP - 2003 Nov TI - Joint manipulation reduces hyperalgesia by activation of monoamine receptors but not opioid or GABA receptors in the spinal cord. PG - 159-68 AB - Joint manipulation has long been used for pain relief. However, the underlying mechanisms for manipulation-related pain relief remain largely unexplored. The purpose of the current study was to determine which spinal neurotransmitter receptors mediate manipulation-induced antihyperalgesia. Rats were injected with capsaicin (50 microl, 0.2%) into one ankle joint and mechanical withdrawal threshold measured before and after injection. The mechanical withdrawal threshold decreases 2 h after capsaicin injection. Two hours after capsaicin injection, the following drugs were administered intrathecally: bicuculline, blocks gamma-aminobutyric acid (GABAA) receptors; naloxone, blocks opioid receptors; yohimbine blocks, alpha2-adrenergic receptors; and methysergide, blocks 5-HT(1/2) receptors. In addition, NAN-190, ketanserin, and MDL-72222 were administered to selectively block 5-HT1A, 5-HT2A, and 5-HT3 receptors, respectively. Knee joint manipulation was performed 15 min after administration of drug. The knee joint was flexed and extended to end range of extension while the tibia was simultaneously translated in an anterior to posterior direction. The treatment group received three applications of manipulation, each 3 min in duration separated by 1 min of rest. Knee joint manipulation after capsaicin injection into the ankle joint significantly increases the mechanical withdrawal threshold for 45 min after treatment. Spinal blockade of 5-HT(1/2) receptors with methysergide prevented, while blockade of alpha2-adrenergic receptors attenuated, the manipulation-induced antihyperalgesia. NAN-190 also blocked manipulation-induced antihyperalgesia suggesting that effects of methysergide are mediated by 5-HT1A receptor blockade. However, spinal blockade of opioid or GABAA receptors had no effect on manipulation induced-antihyperalgesia. Thus, the antihyperalgesia produced by joint manipulation appears to involve descending inhibitory mechanisms that utilize serotonin and noradrenaline. FAU - Skyba, D A AU - Skyba DA AD - Neuroscience Graduate Program, University of Iowa, Iowa City, IA, USA. FAU - Radhakrishnan, R AU - Radhakrishnan R FAU - Rohlwing, J J AU - Rohlwing JJ FAU - Wright, A AU - Wright A FAU - Sluka, K A AU - Sluka KA LA - eng GR - K02 AR002201-05/AR/NIAMS NIH HHS/United States GR - KO2 AR 02201/AR/NIAMS NIH HHS/United States GR - K02 AR002201-01A1/AR/NIAMS NIH HHS/United States GR - R21 AT 001130-02/AT/NCCIH NIH HHS/United States GR - K02 AR002201-03/AR/NIAMS NIH HHS/United States GR - K02 AR002201/AR/NIAMS NIH HHS/United States GR - R21 AT001130-01/AT/NCCIH NIH HHS/United States GR - K02 AR002201-02/AR/NIAMS NIH HHS/United States GR - K02 AR002201-04/AR/NIAMS NIH HHS/United States GR - R21 AT001130-02/AT/NCCIH NIH HHS/United States GR - R21 AT001130/AT/NCCIH NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Pain JT - Pain JID - 7508686 RN - 0 (Adrenergic alpha-Antagonists) RN - 0 (GABA Antagonists) RN - 0 (Narcotic Antagonists) RN - 0 (Receptors, Adrenergic) RN - 0 (Receptors, GABA) RN - 0 (Receptors, Opioid) RN - 0 (Receptors, Serotonin) RN - 0 (Serotonin Antagonists) RN - 2Y49VWD90Q (Yohimbine) RN - 36B82AMQ7N (Naloxone) RN - XZA9HY6Z98 (Methysergide) RN - Y37615DVKC (Bicuculline) SB - IM MH - Adrenergic alpha-Antagonists/pharmacology MH - Animals MH - Bicuculline/pharmacology MH - GABA Antagonists/pharmacology MH - Hyperalgesia/*physiopathology/*therapy MH - Joints/physiology MH - Male MH - Methysergide/pharmacology MH - Naloxone/pharmacology MH - Narcotic Antagonists/pharmacology MH - Pain/physiopathology MH - Pain Management MH - Physical Stimulation MH - *Physical Therapy Modalities MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Adrenergic/*physiology MH - Receptors, GABA/physiology MH - Receptors, Opioid/physiology MH - Receptors, Serotonin/*physiology MH - Serotonin Antagonists/pharmacology MH - Spinal Cord/*physiology MH - Yohimbine/pharmacology PMC - PMC2732015 MID - NIHMS66956 EDAT- 2003/10/29 05:00 MHDA- 2004/01/14 05:00 PMCR- 2009/08/26 CRDT- 2003/10/29 05:00 PHST- 2003/10/29 05:00 [pubmed] PHST- 2004/01/14 05:00 [medline] PHST- 2003/10/29 05:00 [entrez] PHST- 2009/08/26 00:00 [pmc-release] AID - S0304395903003208 [pii] AID - 10.1016/s0304-3959(03)00320-8 [doi] PST - ppublish SO - Pain. 2003 Nov;106(1-2):159-68. doi: 10.1016/s0304-3959(03)00320-8.