Editorial by Robert Gerwin MD of Johns Hopkins Medical School about the Intidyn Fibromyalgia study

Fibromyalgia Is Not All In Your Head, New Research Confirms
Researchers discover a rational biological source of pain in the skin of patients with fibromyalgia

[June 14, 2013, Rensselaer, NY] – 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.

Fibromyalgia is a severely debilitating affliction characterized by widespread deep tissue pain, tenderness in the hands and feet, fatigue, sleep disorders, and cognitive decline. However, routine testing has been largely unable to detect a biological basis for fibromyalgia, and standard diagnosis is based upon subjective patient pain ratings, further raising questions about the true nature of the disease. For many years, the disorder was believed to be psychosomatic (“in the head”) and often attributed to patients’ imagination or even faking illness. Currently approved therapeutics that provide at least partial relief to some fibromyalgia patients are thought to act solely within the brain where imaging techniques have detected hyperactivity of unknown origin referred to as “central sensitization.” However, an underlying cause has not been determined, leaving many physicians still in doubt about the true origins or even the existence of the disorder.

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.

“Instead of being in the brain, the pathology consists of excessive sensory nerve fibers around specialized blood vessel structures located in the palms of the hands,” said Dr. Rice, President of Intidyn and the senior researcher on the study. “This discovery provides concrete evidence of a fibromyalgia-specific pathology which can now be used for diagnosing the disease, and as a novel starting point for developing more effective therapeutics.”

Nerve Endings Come In Many Forms

Three years ago, Intidyn scientists published the discovery of an unknown nervous system function among the blood vessels in the skin in the journal PAIN.

As Dr. Rice explained, “we analyzed the skin of a particularly interesting patient who lacked all the numerous varieties of sensory nerve endings in the skin that supposedly accounted for our highly sensitive and richly nuanced sense of touch. Interestingly however, this patient had surprisingly normal function in day to day tasks. But, the only sensory endings we detected in his skin were those around the blood vessels”. Dr. Rice continued, “We previously thought that these nerve endings were only involved in regulating blood flow at a subconscious level, yet here we had evidencs that the blood vessel endings could also contribute to our conscious sense of touch… and also pain.”

Now, in collaboration with renowned Albany Medical Center neurologist and pain specialist Dr. Charles E. Argoff, the study primary investigator, and his collaborators Dr. James Wymer also at Albany Medical College and Dr. James Storey of Upstate Clinical Research Associates in Albany, NY, clinical research proposals were funded by Forest Laboratories and Eli Lilly. Both pharmaceutical companies have developed FDA-approved medications with similar functions (Serotonin/Norepinephrine Reuptake Inhibitors, SNRI) that provide at least some degree of relief for many fibromyalgia patients.

“Knowing how these drugs were supposed to work on molecules in the brain,” Dr. Albrecht added, “we had evidence that similar molecules were involved in the function of nerve endings on the blood vessels. Therefore, we hypothesized that fibromyalgia might involve a pathology in that location”. As the results demonstrate, they were correct.

To analyze the nerve endings, Drs. Rice, Albrecht, and postdoctoral researcher Dr. Quanzhi Hou, used their unique microscopic technology to study small skin biopsies (less than half the size of a pencil eraser) collected from the palms of fibromyalgia patients, who were being diagnosed and treated by Drs. Argoff, Wymer, and Storey. The study was limited to women, who have over twice the occurrence of fibromyalgia than men. What the team uncovered was an enormous increase in sensory nerve fibers at specific sites within the blood vessels of the skin. These critical sites are tiny muscular valves, called arteriole-venule (AV) shunts, which form a direct connection between arterioles and venules (see diagram).

As Dr. Rice describes their function, “We are all taught that oxygenated blood flows from arterioles to capillaries, which then convey the deoxygenated blood to the venules. The AV shunts in the hand are unique in that they create a bypass of the capillary bed for the major purpose of regulating body temperature.”

A Thermostat for the Skin

In humans, these types of shunts are unique to the palms of our hands and soles of our feet which work like the radiator in a car. Under warm conditions, the shunts close down to force blood into the capillaries at the surface of the skin in order to radiate heat from the body, and our hands get sweaty. Under cold conditions, the shunts open wide allowing blood to bypass the capillaries in order to conserve heat, and our hands get cold and put on gloves.

According to Dr. Albrecht, “the excess sensory innervation may itself explain why fibromyalgia patients typically have especially tender and painful hands. But, in addition, since the sensory fibers are responsible for opening the shunts, they would become particularly active under cold conditions, which are generally very bothersome to fibromyalgia patients.“

A role in regulating blood flow throughout the body.

Although they are mostly limited to the hands and feet, the shunts likely have another important function which could account for the widespread deep pain, achiness, and fatigue that occurs in fibromyalgia patients.

“In addition to involvement in temperature regulation, an enormous proportion of our blood flow normally goes to our hands and feet. Far more than is needed for their metabolism” noted Dr. Rice. “As such, the hands and the feet act as a reservoir from which blood flow can be diverted to other tissues of the body, such as muscles when we begin to exercise. Therefore, the pathology discovered among these shunts in the hands could be interfering with blood flow to the muscles throughout the body. This mismanaged blood flow could be the source of muscular pain and achiness, and the sense of fatigue which are thought to be due to a build-up of lactic acid and low levels of inflammation fibromyalgia patients. This, in turn, could contribute to the hyperactvity in the brain.”

Dr. Albrecht also points out that alterations of normal blood flow may underlie other fibromyalgia symptoms, such as non-restful sleep or cognitive dysfunctions. “The data do appear to fit with other published evidence demonstrating blood flow alterations to higher brain centers and the cerebral cortex of fibromyalgia patients” he stated.

Senior Research Chair of the Alan Edwards Center for Pain Research at McGill University, Dr. Gary Bennett, commented after seeing the results that “It is exciting that something has finally been found. We can hope that this new finding will lead to new treatments for fibromyalgia patients who now receive little or no relief from any medicine.”

This discovery of a distinct tissue pathology demonstrates that fibromyalgia is not “all in your head”, which should provide an enormous relief to fibromyalgia patients, while changing the clinical opinion of the disease and guiding future approaches for successful treatments.

About Integrated Tissue Dynamics LLC (Intidyn)

Integrated Tissue Dynamics LLC (www.Intidyn.com), located in Rensselaer, NY amid the Capital region’s Technology Valley, provides flexible and scalable pre-clinical and clinical research and consulting capabilities on skin and nerve related chronic pain afflictions in collaboration with the pharmaceutical industry, government agencies, academia, and a network of pain specialists throughout the United States. The Intidyn ChemoMorphometric Analysis (CMA) platform can be used to detect chemical and structural changes in the skin and other tissues related to chronic pain, numbness, and itch associated with a wide variety of afflictions, including diabetes, shingles, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy, unintended side effects of pharmaceuticals, and others.

How to Support Further Research on Fibromyalgia and Other Types of Chronic Pain

Tax deductable donations to support the research of a nationwide network of pain specialists, which includes Drs. Argoff and Wymer at Albany Medical College, can be made to the Clinical Pain Research Program at the University of California San Diego, an American Pain Society Center of Excellence, by contacting the UC San Diego Office of Development (giving.ucsd.edu; 858-534-1610; specify area of research) or UC San Diego Center for Pain Medicine (anes-cppm.ucsd.edu; 858-657-7072). This network, referred to informally as the Neuropathic Pain Research Consortium, includes top neurologists, anesthesiologists, and research scientists at leading universities and pain treatment centers in California, Illinois, Maryland, Massachusetts, Minnesota, New York, Utah, Washington, and Wisconsin.

Albrecht PJ, Hou Q, Argoff CE, Storey JR, Wymer JP, Rice FL (2013). 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.

Pain Medicine, May 20. doi: 10.1111/pme.12139 [Epub ahead of print].

Posted at the National Library of Medicine (PubMed): http://www.ncbi.nlm.nih.gov/pubmed/23691965

A description of this study for the general public can be found here.

For further information, contact:

Frank L. Rice, PhD
This email address is being protected from spambots. You need JavaScript enabled to view it.
866-610-7581, ext. 102

Researchers Discover a Rational Source of Pain in Skin of Fibromyalgia Patients: Simplfied Description

Skin Cell Target for Pain Discovered Using Novel Translational Research Platform

June 6, 2011 – (Rensselaer, N.Y., USA) – A new study may explain why only 50% of patients experiencing chronic nerve pain achieve even partial relief from existing therapeutics.i The study, published in the June 6 online version of the international research journal PAIN,ii reveals that certain types of chronic pain may be caused by signals from the skin itself, rather than damage to nerves within the skin, as previously thought.

A Medical Mystery

For years, researchers have known that increased amounts of a molecule called Calcitonin Gene-Related Peptide (CGRP) is found in the skin of chronic pain patients. The source of the increased CGRP was thought to be certain types of sensory nerve fibers in the skin that normally make and release a type or "isoform" called CGRP-alpha. Curiously, however, the authors of the current study found that nerve fibers containing CGRP-alpha are actually reduced under painful conditions – leading them to investigate where the increased CGRP in the skin came from.

The answer, surprisingly, was that the skin cells themselves generate increased amounts of a lesser-known "beta" isoform of CGRP. This skin cell-derived CGRP-beta is increased in painful conditions and may be sending pain signals to remaining sensory nerve fibers in the skin. The discovery of CGRP-beta as a therapeutic target presents a potentially important new treatment approach.

"Since CGRP-alpha normally plays an important role in both the regulation of blood flow and normal inflammatory responses, targeting this molecule as a treatment for chronic pain could cause undesired side-effects on circulation," said the paper's corresponding author, Phillip J. Albrecht, Ph.D., Assistant Professor of Neuroscience at Albany Medical College and Vice President at Integrated Tissue Dynamics, LLC, whose team conducted the research. "However, since we know that these two forms of CGRP are derived from separate genes, we may be able to selectively manipulate the beta isoform without affecting the alpha, and dramatically reduce unwanted toxicities -- a common problem limiting the successful development of novel pain therapeutics. This is really a two-for-one discovery: a novel mechanism we can specifically target in a novel skin location."

The discovery that CGRP-beta from keratinocyte cells of skin may be causing pain has profound implications for the treatment and study of a host of chronic neuropathic pain conditions such as shingles, diabetic neuropathy, and physical injury, which altogether affect approximately 30 million people in the U.S.iii who collectively spend more than $4.5 billion each year to treat chronic nerve pain.iv

A New Translational Research Platform

The present study was a comprehensive translational research project that integrated results from cell culture, animal models of chronic pain and human pain condition tissues to confirm that CRGP is generated in keratinocytes in each of those systems. The study also demonstrates how a translational research platform can be utilized to discover novel targets and provide drug companies with better predictive data that can be used to make time- and cost-reducing decisions early in the drug discovery process.

To observe differences between CGRP in healthy and inflamed or painful skin, the researchers used an imaging methodology called chemomorphometric analysis (CMA), a technique they use to observe, quantify, and characterize molecules like CGRP in the microscopic structure of skin samples half the size of a pencil eraser. A commercially expanded version of the technique, pioneered by Integrated Tissue Dynamics, LLC, interpreted those results and integrated them with assessments of the genetic activity for each CGRP isoform, which led to the discovery that the beta molecule, not the alpha, predominated in keratinocytes.

"We are especially excited by our translational research results because the identification of beta CGRP in keratinocytes will have immediate value in the clinical setting, and also demonstrates how our CMA technology can deliver on the promise of translational medicine," said Frank L. Rice, Ph.D., Professor of Neuroscience at Albany Medical College and CEO at Integrated Tissue Dynamics, LLC. "Furthermore, the identification of beta CGRP in skin keratinocytes may become a useful independent biomarker for the therapeutic effectiveness of chronic neuropathic pain treatments."

The initial discovery stems from the Ph.D. dissertation research of Albany Medical College graduate student Quanzhi Hou, M.D., who is being co-mentored by Drs. Albrecht and Rice, in conjunction with research by Travis Barr, Ph.D., a former graduate student in the lab. Dr. Hou's research was made possible with the support of an international network of researchers and clinicians from Albany Medical College, the Feinberg School of Medicine of Northwestern University, Boston College, the University at Albany, the University of Brescia (Italy), the Israel Institute of Technology, and companies Vertex Pharmaceuticals and Integrated Tissue Dynamics. Dr. Rice noted that "As a co-discovery in the labs of Albany Medical College and Integrated Tissue Dynamics, we are filing a patent to develop our research and commercialization options."

About the Study

The present study found CGRP levels increased in keratinocytes of painful skin from humans with postherpetic neuralgia (PHN) and complex regional pain syndrome type 1 (CRPS). Elevated CGRP levels were also found in skin keratinocytes from monkeys infected with the equivalent of HIV, and in rats with nerve injury and inflammatory pain conditions similar to those caused by accidents and shingles. CGRP was also found in human keratinocyte cell cultures, and the beta isoform predominated.

Previous research has documented abnormally increased levels of CGRP in the skin, blood, and cerebral spinal fluid under a variety of human and animal chronic pain conditions, and CGRP has consequently become a leading target for chronic pain therapeutics. However, prior research has largely not distinguished between the two isoforms and it has been assumed that the increased CGRP seen in previous studies was the alpha isoform generated by nerves that supply sensory innervation to the skin. Recently, members of the Intidyn and the Medical College group also published a pioneering study demonstrating that CGRP (likely alpha) innervation to the blood vessels plays a previously unknown role in normal skin sensation.v The current findings now add to that story, the role of a second (beta) isoform produced in a unique location (keratinocytes) - which likely also plays a critical role in both normal sensation and chronic painful conditions.

About Integrated Tissue Dynamics Chemomorphometric Analysis (ITD-CMA)

ITD-CMA is a proprietary analytic platform that can be used in any complex tissue to determine the effect of treatments, diseases, and toxins on healthy tissue. It was developed into a commercial service to meet increasing demand from pharmaceutical companies for integrated analyses that can identify biomarkers and evaluate potential therapeutic strategies. It is currently used by several leading biotechnology and pharmaceutical companies to identify early-stage indications of side effects and to determine if a treatment is accurately targeting the cause of a disease or symptom.

About Integrated Tissue Dynamics, LLC

Integrated Tissue Dynamics, also called INTIDYN, was established in 2008 by research scientists from Albany Medical College to translate more than 35 years of experience in complex tissue analysis from the laboratory to the development of effective and safe therapeutics. It is a privately-held research and contract services organization located in Rensselaer, N.Y. and serves many of the pharmaceutical industry's leading companies. Learn more at www.Intidyn.com.

About Albany Medical College

Albany Medical Center, northeastern New York's only academic health sciences center, is the largest private employer in the Capital Region. It incorporates the 651-bed Albany Medical Center Hospital, which offers the widest range of medical and surgical services in the region, and the Albany Medical College, which trains the next generation of doctors, scientists and other healthcare professionals, and which also includes a biomedical research enterprise and the region's largest physicians practice with 325 doctors. Albany Medical Center works with dozens of community partners to improve the region's health and quality of life. For more information: www.amc.edu or www.facebook.com/albanymedicalcenter.

Citation: Hou Q, Barr TP, Gee LE, Vickers JT, Wymer JP, Borsani E, Rodella LF, Getsios S, Burdo TH, Eisenberg E, Guha U, Kessler JA, Lavker RM, Chittur S, Fiorino DF, Rice FL, Albrecht PJ. (2011) Keratinocyte Expression of CGRP beta: Implications for Neuropathic and Inflammatory Pain Mechanisms. Pain. 06 June 2011 (10.1016/j.pain.2011.04.033).

Posted at: http://www.painjournalonline.com/article/S0304-3959%2811%2900313-7/abstract

Contacts:

Dr. Frank L. Rice, PhD
This email address is being protected from spambots. You need JavaScript enabled to view it.
8866-610-7581, ext. 102
Integrated Tissue Dynamics (INTIDYN)

Sue Ford
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1-518-262-3421
Albany Medical Center

 

i Dworkin RH, O'Connor AB, Backonja M, et al. "Pharmacologic management of neuropathic pain: evidence-based recommendations". Pain 132 (3): 237–51 (2007). doi:10.1016/j.pain.2007.08.033. PMID 17920770.

ii Hou Q, Barr TP, Gee LE, Vickers JT, Wymer JP, Borsani E, Rodella LF, Getsios S, Burdo TH, Eisenberg E, Guha U, Kessler JA, Lavker RM, Chittur S, Fiorino DF, Rice FL, Albrecht PJ. (2011) Keratinocyte Expression of CGRP: Implications for Neuropathic and Inflammatory Pain Mechanisms. Pain. Posted at: http://www.painjournalonline.com/article/S0304-3959%2811%2900313-7/abstract

iii American Pain Society. Chronic Pain in America: Roadblocks to Relief. http://www.ampainsoc.org/resources/roadblocks/conclude_road.htm. Last accessed May 12, 2011.

iv Conservative calculation based on multiple market estimates. See http://www.pressreleasesworld.com/aarkstore-enterprise-neuropathic-pain-pipeline-assessment-and-market-forecasts-to-2016/

v Bowsher D, Woods CG, Nicholas AK, Carvalho OM, Haggett CE, Tedman B, Mackenzie JM, Crooks D, Mahmood N, Twomey JA, Hann S, Jones D, Wymer JP, Albrecht PJ, Argoff CE, Rice FL. (2009) Absence of pain with hyperhidrosis: a new syndrome where vascular afferents may mediate cutaneous sensation. Pain, 147(1-3): 287-98.

Article in The Business Review

-- Company also Pens Several New R&D Agreements with Biopharmaceutical Industry --

Rensselaer, NY (April 19, 2011) – Integrated Tissue Dynamics, LLC ("INTIDYN") announced today its receipt of a $300,000 award from the National Institute of Neurological Disorders and Stroke (NINDS) as part of the Agency’s Phase I Small Business Technology Transfer (STTR) program.

The STTR program is a highly competitive, three-phase award system that provides qualified small businesses and their academic collaborators with funding to evaluate the scientific and technical merit of an innovative idea. The STTR grant announced today enables INTIDYN to further develop, refine and adapt its proprietary ChemoMorphometric Analysis (ITD-CMA) methodology, which received international attention in December 2009 when it was used to discover a hidden sensory system in the skin.i

"This new grant allows us to assess the unique biochemical causes of pain in post-herpetic neuralgia, a condition certain patients experience after recovering from shingles," said Frank L. Rice, Ph.D., CEO of INTIDYN. "The cause of that pain is a mystery and varies from patient to patient. We expect this new investment in our ITD-CMA technology to generate extremely informative and actionable data that will allow physicians to zero-in on the exact cause of a person’s pain and target it with an appropriate and effective treatment."

The ITD-CMA methodology is a platform technology that is applicable to a wide variety of medical conditions, particularly those that affect the skin and other tissues either directly or as a side effect. INTIDYN has partnered on the STTR with co-Principal investigators and Albany Medical College (AMC) neurologists Charles E. Argoff, M.D., Professor of Neurology, and James Wymer, M.D., Ph.D., Associate Professor of Neurology, who will work directly with patients and help correlate INTIDYN’s data with each patient’s clinical status.

About the Use of ITD-CMA in this Study

Doctors who treat patients with shingles (herpes zoster rash) find that about 30% of people experience chronic pain at the skin site of the healed rash long after all other symptoms have subsided, a condition termed post-herpetic neuralgia (PHN). Unfortunately, doctors do not understand how or why the chronic pain occurs or which patients will develop pain. However, the AMC physicians and INTIDYN scientists believe that by examining skin samples (or "biopsies") from patients who have ongoing pain -- and comparing that skin with skin biopsies from people who have healed -- it will be possible to identify the physical changes taking place inside the skin that cause pain. (The biopsy is about 3mm in diameter, about half the size of a pencil eraser.)

This NINDS grant provides funds for the physicians to obtain the biopsies and for INTIDYN to analyze them using the ITD-CMA platform pioneered by the company. ITD-CMA enables scientists to look at the structure of the skin's nerves and blood vessels and look at the biochemical activity within the skin. INTIDYN scientists look for differences between the chemistry and structure of diseased skin and healthy skin. This type of tissue structure and chemistry information will help lead to a better understanding of the chronic pain mechanisms and to improved treatment options for PHN.

Biopharmaceutical companies utilize ITD-CMA in their research projects because the information generated can be used to spot side effects, infer the way a potential therapeutic drug is interacting with a disease, or monitor what happens in the regular course of disease.

"We will pursue a Phase II STTR grant with results from this study, which will allow us to scale up and make ITD-CMA more powerful and commercially viable," said Dr. Rice. “The results of that Phase of research and the ongoing refinement of our technology are of great interest to the biopharmaceutical industry, so we hope to soon see INTIDYN’s CMA become a mainstream drug target discovery tool."

INTIDYN recently signed ITD-CMA research agreements with several biopharmaceutical companies and is in discussions with others to help those companies develop better therapeutics in a variety of pressing medical conditions.

About Integrated Tissue Dynamics (INTIDYN)

Integrated Tissue Dynamics, LLC, also known as Intidyn (www.Intidyn.com), provides flexible and scalable research capabilities on behalf of pharmaceutical companies to detect chemical and structural changes in the skin. Such changes are associated with the chronic numbness, pain and itch associated with a wide variety of afflictions such as diabetes, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy, vascular conditions and even the unintended side effects caused by many drugs.

Albany Medical College

At Albany Medical College, one of the nation’s oldest medical schools, basic research scientists work to facilitate discoveries that translate into medical innovations at patients’ bedsides. NIH-funded scientists are conducting research in many exciting areas including infectious disease, biodefense, addiction, cancer, pain, and more. Albany Medical Center is northeastern New York's only academic health sciences center. It consists of Albany Medical College, Albany Medical Center Hospital; and the Albany Medical Center Foundation, Inc. Additional information about Albany Medical Center can be found at www.amc.edu.

About NINDS and the NIH

The project described was supported by Award Number 1R41NS070387-01 from the National Institute of Neurological Disorders and Stroke (NINDS) (www.ninds.nih.gov), a component of the National Institutes of Health (NIH). The content in this press release is solely the responsibility of INTIDYN and does not necessarily represent the official view of NINDS or the NIH.

NINDS is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease — a burden borne by every age group, by every segment of society, by people all over the world.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Contact:

Dr. Frank L. Rice, PhD
This email address is being protected from spambots. You need JavaScript enabled to view it.
8866-610-7581, ext. 102
Integrated Tissue Dynamics (INTIDYN)

iBowsher D, et al. Absence of pain with hyperhidrosis: A new syndrome where vascular afferents may mediate cutaneous sensation. PAIN. 2009 Dec 15;147(1-3):287-98

May 04, 2010 (Albany, N.Y., USA )- In the video behind this link, Intidyn Founder Dr. Frank L. Rice introduces a new evidence-based paradigm for thinking about chronic pain and proposes a new approach for its treatment.  He points out how current research on this topic is based on theories of acute pain, which do not adequately explain the causes of chronic pain.  Intidyn’s founders are currently publishing additional evidence in support of this new theory, and you can catch the inside story by clicking the video link below:

Video Link: http://painclinician.com/video/id/57/

About Integrated Tissue Dynamics (INTIDYN)

Integrated Tissue Dynamics, LLC, also known as INTIDYN, provides flexible and scalable research capabilities on behalf of pharmaceutical companies to detect chemical and structural changes in the skin that may cause the chronic numbness, pain and itch associated with a wide variety of afflictions such as diabetes, shingles, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy and even the unintended side effects caused by many drugs. Such afflictions and the associated neurological problems respond poorly to existing treatments.

Contact:

Dr. Frank L. Rice, PhD
This email address is being protected from spambots. You need JavaScript enabled to view it.
8866-610-7581, ext. 102
Integrated Tissue Dynamics (INTIDYN)

April 16, 2010 (Albany, N.Y., USA )- The April 2010 issue of Discover includes an article about Intidyn’s discovery of a hidden sensory system: the nerves regulating blood vessels and sweat glands.  This discovery, published in the international journal PAIN in December 2009, suggests that in addition to regulating blood flow and sweating, the central nervous system (CNS) also is constantly monitoring the biochemistry of the microenvironment surrounding blood vessels as small as capillaries and arterioles.  Further studies have shown that damage to these particular nerves is indicative of damage to the vessels themselves, and suggest that these “hidden” nerves are essential for the health, integrity, and adaptability of the cardiovascular system.  As few studies have been done on the innervation of blood vessels and sweat glands, this finding opens up a whole new area of research and therapeutic promise.  For example, it may in part explain why certain cardiovascular conditions are resistant to current treatment modalities which focus solely on the smooth muscle and blood flow of the blood vessels, without protecting their nerves.  It may also help to establish a physical rationale for mysterious and painful conditions such as migraine and fibromyalgia, the causes of which are currently uncertain.  Intidyn’s research into this area continues, with investigations of cardiovascular innervations in a number of disease indications.    

About Integrated Tissue Dynamics (INTIDYN)

Integrated Tissue Dynamics, LLC, also known as INTIDYN, provides flexible and scalable research capabilities on behalf of pharmaceutical companies to detect chemical and structural changes in the skin that may cause the chronic numbness, pain and itch associated with a wide variety of afflictions such as diabetes, shingles, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy and even the unintended side effects caused by many drugs. Such afflictions and the associated neurological problems respond poorly to existing treatments.

Contact:

Dr. Frank L. Rice, PhD
This email address is being protected from spambots. You need JavaScript enabled to view it.
8866-610-7581, ext. 102
Integrated Tissue Dynamics (INTIDYN)

Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice

March 30, 2010 (Albany, N.Y., USA )- -In this publication with researchers from Harvard, Dana-Farber Cancer Center, and several other institutions, Intidyn founder Frank L. Rice contributes to an important study identifying a likely cause of itch – a poorly understood condition that affects us all. In it, the researchers show that the loss of specific inhibitory neurons – rather than overactivation of itch receptors -- enables persistent itching to occur. The discovery of this mechanism opens important new avenues for the control of chronic pathological itching conditions, in which itch is so intense and unceasing that people and animals with this condition often injure themselves.

Article Link: https://www.cell.com/neuron/abstract/S0896-6273(10)00142-X?script=true   

About Integrated Tissue Dynamics (INTIDYN)

Integrated Tissue Dynamics, LLC, also known as INTIDYN, provides flexible and scalable research capabilities on behalf of pharmaceutical companies to detect chemical and structural changes in the skin that may cause the chronic numbness, pain and itch associated with a wide variety of afflictions such as diabetes, shingles, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy and even the unintended side effects caused by many drugs. Such afflictions and the associated neurological problems respond poorly to existing treatments.

Contact:

Dr. Frank L. Rice, PhD
This email address is being protected from spambots. You need JavaScript enabled to view it.
8866-610-7581, ext. 102
Integrated Tissue Dynamics (INTIDYN)

Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling

February 09, 2010 (Albany, N.Y., USA )- -Intidyn founder Phillip J. Albrecht joins researchers from Albany Medical College, the Wadsworth Center, RPI, and other institutions in this study of how certain opioids reduce pain.  In the study, the researchers show that after activating certain opioid receptors in the brain, cytochrome 450 epoxygenases are released, suggesting a mechanism by which other pain-killers such as morphine and cannabinoids may also lower the perception of pain. 

Article Link: http://www.nature.com/neuro/journal/v13/n3/full/nn.2497.html    

About Integrated Tissue Dynamics (INTIDYN)

Integrated Tissue Dynamics, LLC, also known as INTIDYN, provides flexible and scalable research capabilities on behalf of pharmaceutical companies to detect chemical and structural changes in the skin that may cause the chronic numbness, pain and itch associated with a wide variety of afflictions such as diabetes, shingles, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy and even the unintended side effects caused by many drugs. Such afflictions and the associated neurological problems respond poorly to existing treatments.

Contact:

Dr. Frank L. Rice, PhD
This email address is being protected from spambots. You need JavaScript enabled to view it.
8866-610-7581, ext. 102
Integrated Tissue Dynamics (INTIDYN)

Persons lacking known nerve receptors can still touch and feel; may shed light on causes of unexplained pain such as fibromyalgia

December 15, 2009 (Albany, N.Y., USA )- - The human sensory experience is far more complex and nuanced than previously thought, according to a groundbreaking new study published in the December 15 issue of the journal Pain (http://www.painjournalonline.com/article/S0304-3959%2809%2900526-0/abstract). In the article, researchers at Albany Medical College, the University of Liverpool and Cambridge University report that the human body has an entirely unique and separate sensory system aside from the nerves that give most of us the ability to touch and feel. Surprisingly, this sensory network is located throughout our blood vessels and sweat glands, and is for most people, largely imperceptible.

"It's almost like hearing the subtle sound of a single instrument in the midst of a symphony," said senior author Frank Rice, PhD, a Neuroscience Professor at Albany Medical College (AMC), who is a leading authority on the nerve supply to the skin. "It is only when we shift focus away from the nerve endings associated with normal skin sensation that we can appreciate the sensation hidden in the background."

The research team discovered this hidden sensory system by studying two unique patients who were diagnosed with a previously unknown abnormality by lead author David Bowsher, M.D., Honorary Senior Research Fellow at the University of Liverpool's Pain Research Institute. These patients had an extremely rare condition called congenital insensitivity to pain, meaning that they were born with very little ability to feel pain. Other rare individuals with this condition have excessively dry skin, often mutilate themselves accidentally and usually have severe mental handicaps. "Although they had a few accidents over their lifetimes, what made these two patients unique was that they led normal lives. Excessive sweating brought them to the clinic, where we discovered their severe lack of pain sensation," said Dr. Bowsher. "Curiously, our conventional tests with sensitive instruments revealed that all their skin sensation was severely impaired, including their response to different temperatures and mechanical contact. But, for all intents and purposes, they had adequate sensation for daily living and could tell what is warm and cold, what is touching them, and what is rough and smooth."

The mystery deepened when Dr. Bowsher sent skin biopsies across the ocean to Dr. Rice's laboratory, which focuses on multi-molecular microscopic analyses of nerve endings in the skin, especially in relation to chronic pain conditions such as those caused by nerve injuries, diabetes, and shingles. These unique analyses were pioneered by Dr. Rice at Albany Medical College (AMC) along with collaborators at the Karolinska Institute in Stockholm, Sweden. "Under normal conditions, the skin contains many different types of nerve endings that distinguish between different temperatures, different types of mechanical contact such as vibrations from a cell phone and movement of hairs, and, importantly, painful stimuli," said Dr. Rice. "Much to our surprise, the skin we received from England lacked all the nerve endings that we normally associated with skin sensation. So how were these individuals feeling anything?"

The answer appeared to be in the presence of sensory nerve endings on the small blood vessels and sweat glands embedded in the skin. "For many years, my colleagues and I have detected different types of nerve endings on tiny blood vessels and sweat glands, which we assumed were simply regulating blood flow and sweating. We didn't think they could contribute to conscious sensation. However, while all the other sensory endings were missing in this unusual skin, the blood vessels and sweat glands still had the normal types of nerve endings. Apparently, these unique individuals are able to 'feel things' through these remaining nerve endings," said Dr. Rice. "What we learned from these unusual individuals is that there's another level of sensory feedback that can give us conscious tactile information. Problems with these nerve endings may contribute to mysterious pain conditions such as migraine headaches and fibromyalgia, the sources of which are still unknown, making them very difficult to treat."

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In addition to international collaborations such as this one, Dr. Rice and his principle AMC colleague, Dr. Phillip Albrecht, in the Center for Neuropharmacology and Neuroscience, collaborate extensively with neurologists Dr. Charles Argoff at AMC and Dr. James Wymer of Upstate Clinical Research Associates, who also holds a joint AMC appointment. All are co-authors on the study, which included normal subjects from the Albany, N.Y. area. Several studies on chronic pain are being conducted by this team with support from National Institutes of Heath (NIH) and several pharmaceutical companies.

About Integrated Tissue Dynamics (INTIDYN)

To facilitate these collaborations, Dr. Rice and Dr. Albrecht, recently founded a new biotechnology company, Integrated Tissue Dynamics, LLC, also known as Intidyn (www.Intidyn.com). Intidyn provides flexible and scalable research capabilities on behalf of pharmaceutical companies to detect chemical and structural changes in the skin that may cause the chronic numbness, pain and itch associated with a wide variety of afflictions such as diabetes, shingles, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy and even the unintended side effects caused by many drugs. Such afflictions and the associated neurological problems respond poorly to existing treatments.

"By looking carefully at genomics and the structural and chemical differences between normal and diseased skin, we can better determine if a treatment is working or if it's even targeting the right problem," said Dr. Rice. "For example, in cases of 'unexplained' pain that's unresponsive to conventional treatment, it's important to know if nerve receptors in the vascular and sweat gland tissue are involved, and if so, whether a given treatment is targeting those nerves. We can also see if a pain treatment is damaging vascular tissue, for example, and make inferences about what the impact of that damage might mean clinically."

Most recently, Intidyn has partnered with neurologists and fellow co-authors, Drs. Argoff and Wymer to study a mysterious condition called fibromyalgia. They suspect the unrelenting pain may be related to the sensory nerve endings on blood vessels deep in the skin.

About Albany Medical College

At Albany Medical College, one of the nation's oldest medical schools, basic research scientists work to facilitate discoveries that translate into medical innovations at patients' bedsides. NIH-funded scientists are conducting research in many exciting areas including infectious disease, biodefense, addiction, cancer, pain, and more. Albany Medical Center is northeastern New York's only academic health sciences center. It consists of Albany Medical College, Albany Medical Center Hospital; and the Albany Medical Center Foundation, Inc. Additional information about Albany Medical Center can be found at www.amc.edu.

Citation:

Bowsher D, Geoffrey Woods C, Nicholas AK, Carvalho OM, Haggett CE, Tedman B, Mackenzie JM, Crooks D, Mahmood N, Aidan Twomey J, Hann S, Jones D, Wymer JP, Albrecht PJ, Argoff CE, Rice FL. Absence of pain with hyperhidrosis: A new syndrome where vascular afferents may mediate cutaneous sensation. PAIN. 2009 Dec 15;147(1-3):287-98.

Contact:

Dr. Frank L. Rice, PhD
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8866-610-7581, ext. 102
Integrated Tissue Dynamics (INTIDYN)