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Pain Med. 2013 May 20. doi: 10.1111/pme.12139. [Epub ahead of print]Excessive Peptidergic Sensory Innervation of Cutaneous Arteriole-Venule Shunts (AVS) in the Palmar Glabrous Skin of Fibromyalgia Patients: Implications for Widespread Deep Tissue Pain and Fatigue.
Albrecht PJ, Hou Q, Argoff CE, Storey JR, Wymer JP, Rice FL.
Source
Integrated Tissue Dynamics, LLC, Rensselaer, New York, USA; Center for Neuropharmacology & Neuroscience, Albany Medical College, Albany, New York, USA.
Abstract
OBJECTIVE:
To determine if peripheral neuropathology exists among the innervation of cutaneous arterioles and arteriole-venule shunts (AVS) in fibromyalgia (FM) patients.
SETTING:
Cutaneous arterioles and AVS receive a convergence of vasoconstrictive sympathetic innervation, and vasodilatory small-fiber sensory innervation. Given our previous findings of peripheral pathologies in chronic pain conditions, we hypothesized that this vascular location may be a potential site of pathology and/or serotonergic and norepinephrine reuptake inhibitors (SNRI) drug action.
SUBJECTS:
Twenty-four female FM patients and nine female healthy control subjects were enrolled for study, with 14 additional female control subjects included from previous studies. AVS were identified in hypothenar skin biopsies from 18/24 FM patient and 14/23 control subjects.
METHODS:
Multimolecular immunocytochemistry to assess different types of cutaneous innervation in 3 mm skin biopsies from glabrous hypothenar and trapezius regions.
RESULTS:
AVS had significantly increased innervation among FM patients. The excessive innervation consisted of a greater proportion of vasodilatory sensory fibers, compared with vasoconstrictive sympathetic fibers. In contrast, sensory and sympathetic innervation to arterioles remained normal. Importantly, the sensory fibers express α2C receptors, indicating that the sympathetic innervation exerts an inhibitory modulation of sensory activity.
CONCLUSIONS:
The excessive sensory innervation to the glabrous skin AVS is a likely source of severe pain and tenderness in the hands of FM patients. Importantly, glabrous AVS regulate blood flow to the skin in humans for thermoregulation and to other tissues such as skeletal muscle during periods of increased metabolic demand. Therefore, blood flow dysregulation as a result of excessive innervation to AVS would likely contribute to the widespread deep pain and fatigue of FM. SNRI compounds may provide partial therapeutic benefit by enhancing the impact of sympathetically mediated inhibitory modulation of the excess sensory innervation.
Wiley Periodicals, Inc.
Albrecht PJ, Hou Q, Argoff CE, Storey JR, Wymer JP, Rice FL.
Source
Integrated Tissue Dynamics, LLC, Rensselaer, New York, USA; Center for Neuropharmacology & Neuroscience, Albany Medical College, Albany, New York, USA.
Abstract
OBJECTIVE:
To determine if peripheral neuropathology exists among the innervation of cutaneous arterioles and arteriole-venule shunts (AVS) in fibromyalgia (FM) patients.
SETTING:
Cutaneous arterioles and AVS receive a convergence of vasoconstrictive sympathetic innervation, and vasodilatory small-fiber sensory innervation. Given our previous findings of peripheral pathologies in chronic pain conditions, we hypothesized that this vascular location may be a potential site of pathology and/or serotonergic and norepinephrine reuptake inhibitors (SNRI) drug action.
SUBJECTS:
Twenty-four female FM patients and nine female healthy control subjects were enrolled for study, with 14 additional female control subjects included from previous studies. AVS were identified in hypothenar skin biopsies from 18/24 FM patient and 14/23 control subjects.
METHODS:
Multimolecular immunocytochemistry to assess different types of cutaneous innervation in 3 mm skin biopsies from glabrous hypothenar and trapezius regions.
RESULTS:
AVS had significantly increased innervation among FM patients. The excessive innervation consisted of a greater proportion of vasodilatory sensory fibers, compared with vasoconstrictive sympathetic fibers. In contrast, sensory and sympathetic innervation to arterioles remained normal. Importantly, the sensory fibers express α2C receptors, indicating that the sympathetic innervation exerts an inhibitory modulation of sensory activity.
CONCLUSIONS:
The excessive sensory innervation to the glabrous skin AVS is a likely source of severe pain and tenderness in the hands of FM patients. Importantly, glabrous AVS regulate blood flow to the skin in humans for thermoregulation and to other tissues such as skeletal muscle during periods of increased metabolic demand. Therefore, blood flow dysregulation as a result of excessive innervation to AVS would likely contribute to the widespread deep pain and fatigue of FM. SNRI compounds may provide partial therapeutic benefit by enhancing the impact of sympathetically mediated inhibitory modulation of the excess sensory innervation.
Wiley Periodicals, Inc.
Fibromyalgia, a painful condition affecting approximately 10 million people in the U.S., is not imaginary after all, as some doctors have believed. A discovery, published this month in PAIN MEDICINE (the journal of the American Academy of Pain Medicine), clearly now demonstrates that fibromyalgia may have a rational biological basis located in the skin.....
...Now, a breakthrough discovery by scientists at Integrated Tissue Dynamics LLC (Intidyn), as part of a fibromyalgia study based at Albany Medical College, has provided a biological rationale for this enigmatic disease. The small biotechnology research company, founded by neuroscientists Dr. Frank L. Rice and Dr. Phillip J. Albrecht, reports on a unique peripheral neurovascular pathology consistently present in the skin of female fibromyalgia patients which may be a driving source of the reported symptoms.
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