Document Detail

Heat, but not mechanical hyperalgesia, following adrenergic injections in normal human skin.
MedLine Citation:
PMID:  11166966     Owner:  NLM     Status:  MEDLINE    
The development of adrenergic sensitivity in nociceptors has been suggested as a mechanism of neuropathic pain. We sought to determine if nociceptors in the skin of normal subjects exhibit adrenergic sensitivity. We investigated the effects of intradermal administration of norepinephrine, phenylephrine, and brimonidine on heat pain sensitivity. Norepinephrine and phenylephrine (in concentrations ranging from 0.1 to 10 microM by factors of 10), brimonidine (at 0.01-1 microM), and saline were injected (30 microl volume) in a random, double-blind manner to different sites on the volar surface of the forearm in ten subjects. Before and after the injections, heat testing was performed with a non-contact laser thermal stimulator. Heat pain threshold was measured by means of a 'Marstock' technique in which subjects pressed a reaction time key when they perceived that a slowly increasing heat stimulus (1 degrees C/s ramp from a 36 degrees C base) was painful. In addition, the subjects used magnitude estimation techniques to rate the intensity of pain to a suprathreshold heat stimulus (47 degrees C, 2 s). Mechanical testing was done using 200-microm diameter probes attached to calibrated weights that provided forces over the range of 16-512 mN. The intradermal injections of norepinephrine, phenylephrine and brimonidine produced little evoked pain. However, a dose-dependant decrease in heat pain threshold, but not mechanical pain threshold, was observed. At the highest drug dose injected, all three adrenergic compounds produced a significant decrease in heat pain threshold compared to the saline injection. A significant increase in response to the suprathreshold heat stimulus was also found. One possible explanation for this apparent heat hyperalgesia is that the decrease in perfusion due to the localized vasoconstriction may alter the heat response. However, in control studies we found that the non-adrenergic vasoconstrictors, angiotensin II and vasopressin did not produce heat hyperalgesia at doses that produced comparable decreases in blood flow. In addition, occlusion of blood flow with a blood pressure cuff did not lead to heat hyperalgesia. Thus, the heat hyperalgesia observed with the adrenergic agonists is not due to a decrease in perfusion associated with the injection. These results indicate that alpha(1)- and alpha(2)-adrenoceptor-mediated mechanisms may play a role in sensitization of nociceptors to heat stimuli in normal skin.
P N Fuchs; R A Meyer; S N Raja
Related Documents :
20001646 - Acid hypersensitivity in patients with eosinophilic oesophagitis.
16247056 - Abnormal forebrain activity in functional bowel disorder patients with chronic pain.
6843906 - Morphine blocks the increase in acid phosphatase in the substantia gelatinosa during pain.
14583386 - Vagus nerve stimulation attenuates heat- and formalin-induced pain in rats.
22985076 - Spinal cord stimulation (scs) in conjunction with peripheral nerve field stimulation (p...
11790476 - Cognitions, coping and social environment predict adjustment to phantom limb pain.
Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pain     Volume:  90     ISSN:  0304-3959     ISO Abbreviation:  Pain     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-05-31     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7508686     Medline TA:  Pain     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  15-23     Citation Subset:  IM    
Department of Neurosurgery, Johns Hopkins University, 5-109 Meyer Bldg., 600 N. Wolfe Street, Baltimore, MD 21287, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adrenergic alpha-Agonists / pharmacology*
Analysis of Variance
Dose-Response Relationship, Drug
Double-Blind Method
Hot Temperature*
Hyperalgesia* / chemically induced
Middle Aged
Nociceptors / drug effects*,  physiology
Norepinephrine / pharmacology
Pain Threshold / drug effects*
Phenylephrine / pharmacology
Quinoxalines / pharmacology
Receptors, Adrenergic / drug effects,  physiology
Skin / drug effects*
Vasoconstrictor Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Quinoxalines; 0/Receptors, Adrenergic; 0/Vasoconstrictor Agents; 51-41-2/Norepinephrine; 59-42-7/Phenylephrine; 59803-98-4/brimonidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Effects of the potent analgesic enkephalin-catabolizing enzyme inhibitors RB101 and kelatorphan on r...
Next Document:  GABAergic modulation of descending inhibitory systems from the rostral ventromedial medulla (RVM). D...