Invented by Luda B. Diatchenko, William Maixner, Gary D. Slade, Andrea Gail Neely, University of North Carolina at Chapel Hill

The market for methods, materials, and methods for determining pain sensitivity, predicting, and treating related disorders is growing rapidly. Pain is a complex and multifaceted phenomenon that affects millions of people worldwide. Chronic pain is a major public health problem that is associated with significant morbidity, disability, and healthcare costs. Therefore, there is a growing need for effective methods and materials for determining pain sensitivity, predicting, and treating related disorders. One of the key drivers of the market for methods, materials, and methods for determining pain sensitivity, predicting, and treating related disorders is the increasing prevalence of chronic pain. According to the American Academy of Pain Medicine, chronic pain affects more than 100 million Americans and costs the US economy more than $600 billion annually. This has led to a growing demand for effective pain management solutions, including methods and materials for determining pain sensitivity, predicting, and treating related disorders. Another key driver of the market is the growing awareness of the importance of personalized medicine. Personalized medicine involves the use of genetic, genomic, and other molecular data to tailor treatments to individual patients. This approach has been shown to be effective in many areas of medicine, including cancer treatment, and is now being applied to pain management. Methods and materials for determining pain sensitivity, predicting, and treating related disorders are an important part of personalized pain management. The market for methods, materials, and methods for determining pain sensitivity, predicting, and treating related disorders is also being driven by advances in technology. For example, the development of new imaging techniques, such as functional magnetic resonance imaging (fMRI), has enabled researchers to study the neural mechanisms of pain and to develop new treatments based on this knowledge. Similarly, advances in genetics and genomics have led to the identification of genetic factors that influence pain sensitivity and response to treatment. There are many companies and organizations that are active in the market for methods, materials, and methods for determining pain sensitivity, predicting, and treating related disorders. These include pharmaceutical companies, medical device manufacturers, and academic research institutions. Many of these companies are developing new drugs, devices, and diagnostic tests that are designed to improve pain management and reduce the burden of chronic pain. In conclusion, the market for methods, materials, and methods for determining pain sensitivity, predicting, and treating related disorders is growing rapidly. This growth is being driven by the increasing prevalence of chronic pain, the growing awareness of the importance of personalized medicine, and advances in technology. As the market continues to grow, we can expect to see new and innovative solutions that will improve pain management and reduce the burden of chronic pain for millions of people worldwide.

The University of North Carolina at Chapel Hill invention works as follows

Methods for treating somatosensory disorder and modulating proinflammatory cytokines are provided. These methods include administering an effective amount of a COMT, ADRB2 or ADRB3 modulator to a subject. Further, methods are provided for predicting the effectiveness of pharmacological treatments for a subject suffering from a somatosensory disorder. This is done by determining the genotype of the subject in relation to a selected gene from the group of ADRB2, ADRB3, or combinations thereof. Further, methods of determining pain response or pain perception, and predicting susceptibility to related disorders such as somatization and somatosensory disorders are provided. This is done by determining the genotype of the subject based on a gene from the group of COMT, ADRB2, ADRB3, or combinations thereof.

Background for Methods, materials and methods for determining pain sensitivity, predicting and treating related disorders.

A person’s pain sensitivity is affected by many environmental and genetic factors” (Mogil (1999). While it is not clear how genetic and environmental factors affect human pain sensitivity, the reported heritability of nociceptive or analgesic sensitivity in mice ranges from 28% to 76% (Mogil (1999). Although animal studies have identified a number of potential?pain genes, there are not many candidate genes. Only a handful of genes have been found to be associated with pain perception in humans.

An understanding the neurobiological and psychological mechanisms that lead to increased pain sensitivity and the risk for developing somatosensory disorder are starting to emerge” (FIG. 1). Central nociceptive pathways’ ability to respond to peripheral input better depends on not only the activity in peripheral primary afferents but also the activity in central pain regulatory system. The interaction between peripheral afferent inputs and central nervous system regulatory networks modulates central neural network activity and produces dynamic, time dependent alterations in excitability and response characteristics for spinal and supraspinal neuro and glia cells that react to noxious stimuli. An abnormal neural processing of noxious stimuli or psychological dysfunction can lead to increased pain sensitivity, and increase the risk of developing somatosensory disorder (FIG). These disorders are hard to diagnose and treat. 1).

The psychological and biological determinants of pain sensitivity, and other somatosensory conditions, are affected by both genetic and environmental factors. Effective treatments require a deeper understanding of the genetic factors that underlie them. There is a need to better understand the genetic variation in molecular pathways that mediate pain sensitivity variations. This knowledge would be valuable in diagnosing and treating pain perception disorders.

One embodiment of the currently disclosed subject matter provides methods for treating a somatosensory problem in a subject.” The method may include administering an effective amount to the subject of an ADRB2 or ADRB3 modulator or any combination thereof.

In some embodiments, the subject is administered both the ADRB2 antagonist as well as the ADRB3 antagonist.

In some embodiments, methods include determining the genotype of a subject relative to a gene selected in the group consisting ADRB2, ADRB3, COMT and combinations thereof, administering to the subject an effective amount of the COMT modator, ADRB2 modulator or ADRB3 modulator based on the subject’s determined genotype.

In some embodiments, the subject’s determined genotype with respect to ADRB2 may be selected from a group that includes two copies each of Haplotype 2 or Haplotype 3 and one copy each of Haplotype 2 or Haplotype 3. At least one copy of Uncommon is also included. The subject is then administered the ADRB2 modator, the COMT modulator or combinations thereof.

In some embodiments, the determined genotype for the subject with regard to ADRB3 is chosen from the group consisting at least two copies of Haplotype 1 and at most one copy of Uncommon. The subject is then treated by administering the ADRB3 or COMT modulator to him/her, or combinations thereof.

In some embodiments, the determined genotype with respect to COMT of the subject is selected from the group consisting two copies APS, two copy of HPS, one copy each of APS and HPS. The somatosensory disorder and COMT modulator are administered to the subject by administering the ADRB2 or ADRB3 modulators, or combinations thereof.

Another embodiment provides a method for predicting the susceptibility of a subject in developing a somatosensory disorders. The method includes determining the subject’s genotype with respect to a gene from the group consisting ADRB2, ADRB3, COMT and combinations thereof. Next, the subject is compared with at least one reference genetic to predict whether or not they will develop the somatosensory disorders.

In some embodiments, the subject’s determined genotype with respect to ADRB2 may be selected from a group that includes two copies each of Haplotype 1 and Haplotype 2, two copies each of Haplotype 3 and Haplotype 4, one copy each of Haplotype 2 or 3, and at most one copy Uncommon. The subject is expected to be susceptible to developing the somatosensory disorders.

In some embodiments, the subject’s determined genotype with respect to ADRB3 may be selected from a group that includes two copies of Haplotype 1 and at least one copy Uncommon. The subject is expected to be susceptible to developing the somatosensory disorders.

In some embodiments, the subject’s determined genotype with respect to COMT may be selected from a group that includes two copies of APS, two copy of HPS and one copy each of APS and HPS. The subject is expected to be at risk of developing the somatosensory disorders.

In one embodiment, methods for predicting pain response in a subject” are provided. The method includes determining the genotype for the subject relative to a gene from the group consisting ADRB2, ADRB3, COMT and combinations thereof. Next, the subject’s genotype is compared with at least one reference genotype associated in pain response variability. This reference genotype can be either an ADRB2 genotype or an ADRB3 genotype.

In some embodiments, there is only one copy Haplotype 1 of ADRB2, and the subject is predicted not to feel as sensitive to pain as the population norm.

In some embodiments, the subject’s determined genotype with respect to ADRB3 may be selected from the group consisting at least one copy Haplotype 2 or at least one Copy of Haplotype 3. The subject is predicted to have decreased pain sensitivity compared to the population norm.

In some embodiments, the subject’s determined genotype with respect to COMT can be selected from a group that includes two copies each of APS and two copies each of HPS. The subject is expected to feel more pain than a population norm.

In one embodiment, methods for predicting somatization are provided. The method includes determining the genotype for the subject based on a gene from the group consisting ADRB2, ADRB3, and COMT. Also, comparing the genotype with at least one reference genotype associated to somatization.

In some embodiments the determined genotype for the subject with regard to ADRB2 are two copies of Haplotype 2. The subject is predicted have greater somatization than a population norm.

In some embodiments the subject’s determined genotype with respect to ADRB3 may be at least one copy Haplotype 3. The subject is expected to have lower somatization than a population norm.

In some embodiments, the determined genotype with respect to COMT of the subject is selected from the group consisting two copies APS, two copy of HPS, one copy each of APS and HPS. The subject is expected to have a higher somatization than a population norm.

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