chemical structure of ketanserin
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Ketanserin

Ketanserin is a serotonin receptor antagonist. It has the highest affinity for the serotonin 5-HT2A receptor, but also binds less potently to the 5-HT2C, 5-HT2B, 5-HT1D, alpha-adrenergic, and dopamine receptors. With tritium radioactively labeled ketanserin is used as a radioligand for the serotonin 5-HT2A receptor, e.g. in receptor binding assays.

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JOURNAL REVIEW
From Journal of the American Chiropractic Association, 5/1/04 by Wyatt, Lawrence H

JOURNAL REVIEW

An exploratory study of provocation testing with padded wedges: Can prone blocking demonstrate a directional preference?

Lisi AJ, Cooperstein R, Morschhauser E J Manipulative Physiol Ther 2004 Feb;27(2):103-8.

BACKGROUND: Currently, no traditional chiropractic examination method to determine a spinal listing offers demonstrated guidance in treatment decisions for low-back pain (LBP) patients. Development of an examination that bypasses the difficult/ of accurately and reliably identifying a listing, yet provides guidance on manipulative vectors, could be very valuable to clinicians and patients.

OBJECTIVE: To explore two potential protocols for provocation testing and assessment of directional preference

METHODS: Two groups of 20 subjects were examined while lying prone on various positions of padded wedges. In the first group, the pain pressure threshold (PPT) was measured at four anatomic points; in the second group, tenderness was measured at one anatomic point.We investigated whether either method could demonstrate a directional preference

RESULTS: When tenderness was measured at one anatomic point, 70% of subjects demonstrated a directional response, and only one subject exhibited an increase in baseline tenrderness at the end of the procedure. When PPT was measured at four anatomic points, 40% of subjects demonstrated a directional response, but 12 subjects exhibited decreased PPT at the end of the procedure.

CONCLUSION: Measuring changes in tenderness at one anatomic point in response to various padded wedge patterns appears promising as an examination procedure to determine directional preference.

COMMENT: This study identifies a potential diagnostic procedure that could supplant the unreliable procedures that some currently use to determine directional forces. Wedges were placed in the anterior pelvic and intertrochanteric regions in four different patterns. Other studies have suggested similar directional preferences with low-back pain. I was left with one question after reading this paper What would the clinical outcome be if the patient were simply left in the posture of directional preference? This research forms the base for some interesting further studies.

Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia.

Banic B, Petersen-Felix S.Andersen OK, Radanov BR Villiger PM.Arendt-Nielsen L, Curatolo M. Pain 2004 Jan; 107(1-2)7-15.

Patients who have chronic pain after whiplash injury or those with fibromyalgia display exaggerated pain after sensory stimulation. Because evident tissue damage is usually lacking, this exaggerated pain perception could be explained by hyperexcitability of the central nervous system.The nociceptive withdrawal reflex (a spinal reflex) may be used to study the excitability state of spinal cord neurons.We tested the hypothesis that patients with chronic whiplash pain and fibromyalgia display facilitated withdrawal reflex and, therefore, spinal cord hypersensitivity.Three groups were studied: whiplash (n=27), fibromyalgia (n=22), and healthy controls (n=29).Two types of transcutaneous electrical stimulation of the sural nerve were applied: single stimulus and five repeated stimuli at 2 Hz. Electromyography was recorded from the biceps femoris muscle.The main outcome measurement was the minimum current intensity eliciting a spinal reflex (reflex threshold). Reflex thresholds were significantly lower in the whiplash, compared with the control group, after both single (P=0.024) and repeated (P=0.035) stimulation.The same was observed for the fibromyalgia group after both stimulation modalities (P=0.001 and 0.046, respectively).We provide evidence for spinal cord hyperexcitability in patients with chronic pain after whiplash injury and in fibromyalgia patients.This can cause exaggerated pain following low-intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain, at least in part, pain in the absence of detectable tissue damage.

Comment: This is a fascinating study that attempts to explain the unusual levels of pain seen in some whiplash and fibromyalgia patients. The authors suggest that the spinal cord becomes overexcitable to the point that stimuli that would not normally cause pain may do so in these patient groups. Further work in this area may have an impact on how these patients are managed, and the results may even affect reimbursement in some of these cases. The challenge will be to study therapies that may have a central effect.

Joint manipulation reduces hyperalgesia by activation of monoamine receptors, but not opioid or GABA receptors in the spinal cord.

Skyba DA, Radhakrishnan R, Rohlwing JJ, Wright A, Sluka KA. Pain 2003 Nov; 106(1-2): 159-68.

Joint manipulation has long been used for pain relief. The underlying mechanisms for manipulation-related pain relief, however, 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 the mechanical withdrawal threshold was 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(I/2) receptors. In addition, NAN190, ketanserin, and MDL-72222 were administered to selectively block 5-HTIA,5-HT2A,and 5-HT3 receptors, respectively. Knee joint manipulation was performed 15 minutes 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 I 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(I/2) receptors with methysergide prevented, while blockade of alpha2adrenergic receptors attenuated, the manipulation-induced antihyperalgesia. NAN-190 also blocked manipulationinduced antihyperalgesia, suggesting that effects of methysergide are mediated by 5-HTIA receptor blockade. Spinal blockade of opioid or GABAA receptors, however, had no effect on manipulationinduced antihyperalgesia.Thus, the antihyperalgesia produced by joint manipulation appears to involve descending inhibitory mechanisms that utilize serotonin and noradrenaline.

Comment: While there are obvious limitations to this study (e.g., extrapolation from rats to humans, the type of manipulation performed, etc.), this is fascinating baseline work, particularly in light of the central hypersensitivity seen in the whiplash and fibromyalgia patients noted above. It appears that the effects of manipulation may be more complex than originally thought

Facet Joint Kinematics and Injury Mechanisms during Simulated Whiplash.

Pearson.Adam M. BA; Ivancic, Paul C. MPhil, lto, Shigeki MD; Panjabi, Manohar M. PhD. Spine Volume 29(4) 15 February 2004 pp 390-397.

Study Design. Facet joint kinematics and capsular ligament strains were evaluated during simulated whiplash of whole cervical spine specimens with muscle force replication.

Objectives. To describe facet joint kinematics, including facet joint compression and facet joint sliding, and quantify peak capsular ligament strain during simulated whiplash.

Summary of Background Data. Clinical studies have implicated the facet joint as a source of chronic neck pain in whiplash patients. Prior in vivo and in vitro biomechanical studies have evaluated facet joint compression and excessive capsular ligament strain as potential injury mechanisms. No study has comprehensively evaluated facet joint compression, facet joint sliding, and capsular ligament strain at all cervical levels during multiple whiplash simulation accelerations.

Methods. The whole cervical spine specimens with muscle force replication model and a bench-top trauma sled were used in an incremental trauma protocol to simulate whiplash of increasing severity. Peak facet joint compression (displacement of the upper facet surface toward the lower facet surface), facet joint sliding (displacement of the upper facet surface along the lower facet surface), and capsular ligament strains were calculated and compared to the physiologic limits determined during intact flexibility testing.

ReSUltS. Peak facet joint compression was greatest at C4-C5, reaching a maximum of 2.6 mm during the 5 g simulation. Increases over physiologic limits (P

Conclusions. Facet joint components may be at risk for injury due to facet joint compression during rear-impact accelerations of 3.5 g and above. Capsular ligaments are at risk for injury at higher accelerations.

Comment: Given that the typical g forces in a motor vehicle accident can be up to 5 g at 5 miles per hour, this study suggests that portions of the facet joints may actually be damaged in low-speed rearend collisions.This is important information, although the study is obviously limited in that it was performed in vitro.

By Lawrence H. Wyatt, DC, DACBR

Dr. Wyatt is a professor in the division of clinical sciences, Texas Chiropractic College, Pasadena, Texas.

Copyright American Chiropractic Association May 2004
Provided by ProQuest Information and Learning Company. All rights Reserved

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