Feng, Qingping

Teasell, Robert W.

English

Scholarship@Western

Western University Scholarship@Western Paediatrics Publications Paediatrics Department 1-1-2015 Hypersensitivity of vascular alpha-adrenoceptor responsiveness: A possible inducer of pain in neuropathic states Robert W. Teasell Lawson Health Research Institute Qingping Feng Schulich School of Medicine & Dentistry Follow this and additional works at: https://ir.lib.uwo.ca/paedpub Citation of this paper: Teasell, Robert W. and Feng, Qingping, "Hypersensitivity of vascular alpha-adrenoceptor responsiveness: A possible inducer of pain in neuropathic states" (2015). Paediatrics Publications. 1230. https://ir.lib.uwo.ca/paedpub/1230 165NEURAL REGENERATION RESEARCH January 2015,Volume 10,Issue 1 www.nrronline.orgLETTERS TO THE EDITORHypersensitivity of vascular alpha-adrenoceptor responsiveness: a possible inducer of pain in neuropathic statesDear editor,Dr. Peter Drummond’s article noted that peripheral nerve and tissue injury in neuropathic pain syndromes releases cytokines which in turn lead to an increase in alpha1-adrenoceptor upreg-ulation, resulting in a heightened sensitivity to noradrenaline. In these circumstances, noradrenaline acting on upregulated alpha1 a-adrenoceptors increases the release of cytokine interleukin-6. Hence, nociceptive afferent neurons exposed to injury induced cytokines become more hypersensitive to noradrenaline, which in turn promotes the release of more inflammatory cytokines. Dr. Drummond noted that this mechanism may contribute to the pain of post-herpetic neuralgia or complex regional pain syn-drome (Drummond, 2014). Using a technique that allowed us to monitor vasoconstriction in peripheral veins of affected limbs in response to increasing concentrations of noradrenaline in local intravenous infusions, we were able to determine the responsiveness of alpha-adreno-ceptors in a number of painful conditions. We found significant venous alpha-adrenoceptor hyperresponsiveness in complex re-gional pain syndrome  (Arnold et al., 1993), spinal cord injuries (Arnold et al., 1995; Teasell et al., 2000) and diabetic peripheral nerve injuries (Capes et al., 1997) to local intravenous infusions of noradrenaline.A similar technique in insulin dependent diabetic mellitus pa-tients found vascular (venous) responsiveness to noradrenaline directly correlated with nerve conduction velocity, a measure of the severity of the nerve injury (Eichler et al., 1992; Bodmer et al., 1999). Notably, the ED50 (defined as the concentration of noradrenaline required to cause a 50% reduction of the resting vein diameter) of the dorsal veins of insulin dependent diabetic mellitus  patients with symptomatic autonomic dysfunction was lower than in asymptomatic diabetics. The exaggerated vascular reactivity to noradrenaline can be blocked by an alpha 1-adre-noceptor blocker doxazosin, suggesting the vascular response is mediated by alpha-1 adrenoceptors. One hypothesis which may account for these findings is a dys-functional sympathetic nervous system with diminished ability of alpha-2 adrenoceptors to presympathetically reuptake nor-adrenaline resulting in excessive stimulation of the alpha-1 ad-renoceptor. Support for this comes from observations of higher noradrenaline levels in patients with a clinical diabetic peripheral neuropathy (Capes et al., 1997) and the fact that transdermal clonidine (an alpha-2-adrenoceptor agonist) is more effective than controls in reducing the pain of peripheral diabetic neurop-athies (Zeigler et al., 1992).This additional evidence, which demonstrates alpha-adreno-ceptor hyperresponsiveness of peripheral veins in three painful neuropathic states, insulin dependent diabetic mellitus, spinal cord injuries and diabetic peripheral neuropathies, raises the in-triguing possibility that sympathetic nervous system dysfunction may be an important factor in the generation of pain in a num-ber of neuropathic states (Teasell and Arnold, 2004). This is also supported by the fact that alpha-adrenoceptor blockers relieve pain in diabetic neuropathy in rodents (Lee et al., 2000; Bujalska et al., 2008) and in patients with chronic prostatitis/chronic pel-vic pain syndrome (Thakkinstian et al., 2012).Robert W. Teasell*, Qingping FengAging, Rehabilitation, and Geriatric Care, Lawson Health Research Institute, St. Joseph’s Parkwood Institute, London, Ontario, Canada (Teasell RW)Department of Physical Medicine and Rehabilitation, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (Teasell RW)Departments of Physiology & Pharmacology, and Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (Feng Q)*Correspondene to: Robert W. Teasell, Robert. Teasell@sjhc.london.on.ca.Accepted: 2014-11-20doi:10.4103/1673-5374.150728          http://www.nrronline.org/Teasell RW, Feng Q (2015) Hypersensitivity of vascular alpha-adreno-ceptor responsiveness: a possible inducer of pain in neuropathic states. Neural Regen Res 10(1):165.                                                                                             ReferencesArnold JM, Feng QP, Delaney GA, Teasell RW (1995) Autonomic dysreflexia in tetraplegic patients: evidence for alpha-adrenoceptor hyperresponsive-ness. Clin Auton Res 5:267-270.Arnold JM, Teasell RW, MacLeod AP, Brown JE, Carruthers SG (1993) Al-tered venous alpha-adrenoceptor responsiveness in patients with reflex sympathetic dystrophy. Annals Intern Med 118:619-621.Bodmer CW, Lake D, Savage MW, Williams G (1999) Hand vein respons-es to noradrenaline in normotensive patients with insulin-dependent diabetes mellitus and microalbuminuria: effects of alpha-adrenoceptor blockade with doxazosin. Curr Med Res Opin 15:169-176.Bujalska M, Araźna M, Makulska-Nowak H, Gumułka SW (2008) Alpha1 and alpha2-adrenoreceptor antagonists in streptozotocin- and vincris-tine-induced hyperalgesia. Pharmacol Rep 60:499-507.Capes S, Teasell RW, Simon J, Finestone H, Arnold JM (1997) Alpha-ad-renoceptor hyperresponsiveness in painful diabetic neuropathy. 57th Annual Scientific Sessions of the American Diabetes Association, Boston, Massachusetts, June 21-24.Drummond PD (2014) Neuronal changes resulting in upregulation of alpha-1 adrenoceptors after peripheral nerve injury. Neural Regen Res 9:1337-1340.Eichler HG, Blaschke TF, Kraemer FB, Ford GA, Blöchl-Daum B, Hoffman BB (1992) Responsiveness of superficial hand veins to alpha-adreno-ceptor agonists in insulin-dependent diabetic patients. Clin Sci (Lond) 82:163-168.Lee YH, Ryu TG, Park SJ, Yang EJ, Jeon BH, Hur GM, Kim KJ (2000) Al-pha1-adrenoceptors involvement in painful diabetic neuropathy: a role in allodynia. Neuroreport 11:1417-1420.Teasell RW, Arnold JM (2004) Alpha-adrenoceptor-1 hyperresponsiveness in three neuropathic pain states: complex regional pain syndrome 1, dia-betic peripheral neuropathic pain and central pain states following spinal cord injury. Pain Res Manag 9:89-97.Teasell RW, Arnold JM, Krassioukov A, Delaney GA (2000) Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil 81:506-16.Thakkinstian A, Attia J, Anothaisintawee T, Nickel JC (2012) Alpha-block-ers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome. BJU Int 110:1014-1022.Zeigler D, Lynch SA, Muir J, Benjamin J, Max MB (1992) Transdermal clon-idine versus placebo in painful diabetic neuropathy. Pain 48:403-408. 

Hypersensitivity of vascular alpha-adrenoceptor responsiveness: A possible inducer of pain in neuropathic states

https://ir.lib.uwo.ca/cgi/viewcontent.cgi?article=2238&context=paedpub

Hypersensitivity of vascular alpha-adrenoceptor responsiveness: A possible inducer of pain in neuropathic states

Abstract

Similar works

Full text

Available Versions

Scholarship@Western