Pain and Addiction Research
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Pain
Pain is a complex and multi-dimensional experience influenced by biological, psychological, and social factors. Although pain is a universal human experience, our understanding of pain is constantly evolving. For centuries, pain was seen as an inevitable part of life that had to be endured. However, pain research has shown that pain is not necessarily beneficial and can even be harmful. In addition, pain research has also revealed that pain is not always an accurate measure of tissue damage. As our understanding of pain has increased, so has our ability to treat it effectively.
Fig.1 Biopsychosocial model of pain. (Vaughn, et al., 2019)
Addiction
Addiction is a chronic brain disease that affects millions of people worldwide. Although addiction has traditionally been viewed as a moral failing, research has shown that it is a severe medical condition with profound implications for public health. Addiction is characterized by compulsive drug seeking and use despite negative consequences, and it often leads to disability and premature death. Despite the high cost of addiction, effective treatments can help people recover from this disease.
A growing body of evidence suggests that chronic pain and addiction are interconnected. Chronic pain is one of the most common reasons people seek addiction treatment.
Fig.2 The cycle of addiction. (Moss-King, 2016)
Membrane Proteins Involved in Pain and Addiction Research
- Sigma-1 Receptor (σ1R)
The σ1R is a ubiquitously expressed protein implicated in the treatment of a number of neurological conditions including stroke, neurodegenerative disease, psychiatric disorders, and neuropathic pain. At the cellular level, the σ1R is located at the endoplasmic reticulum (ER) membrane where it possesses chaperone activity in response to misfolded proteins. Upon activation, the σ1R acts as an intracellular signaling modulator, regulating a variety of cellular functions. Interestingly, a variety of σ1R ligands modulate dopamine neurotransmission and reduce the behavioral effects of METH (methamphetamine) in animal models of addictive behavior, suggesting that the σ1R may be a potential target for the treatment of METH addiction.
Fig.3 Schematic of σ1R receptor cellular activity. (Sambo, et al., 2018)
- Sigma-2 Receptor (σ2R)
Pain and addiction are two of the most common and costly conditions that plague society today. Despite their prevalence, there is still a lack of these conditions. A better understanding of pain and addiction could lead to more effective treatments. One potential interest for pain and addiction research is the σ2R. The σ2R is a membrane protein that is involved in pain signaling. Studies have shown that σ2R is upregulated in areas of the brain associated with pain and addiction. In addition, σ2R is a potential target for pain and addiction treatment. σ2R inhibitors have been shown to reduce pain and addictive behavior in animal models. These findings suggest that σ2R may be a promising pain and addiction treatment target.
- Opioid Receptors
Opioid receptors are found in both the brain and the nervous system and play a key role in pain perception. When opioids bind to these receptors, they reduce the perception of pain. However, they also have other effects, such as feelings of euphoria and relaxation. These effects can lead to abuse and addiction. Therefore, treatments for chronic pain often target these receptors to reduce pain without causing other potentially harmful effects.
Fig.4 Sites of action of opioid analgesics. (Al-Hasani & Bruchas, 2011)
References
- Vaughn, I.; et al. Multispecialty opioid risk reduction program targeting chronic pain and addiction management in veterans. Federal practitioner for the health care professionals of the VA, DoD, and PHS. 2019, 36(9): 406-411.
- Moss-King, D. Addiction psychology. Introduction to Applied Behavioral Science. 2016, 5: 117-139.
- Sambo, D.O.; et al. The sigma-1 receptor as a regulator of dopamine neurotransmission: a potential therapeutic target for methamphetamine addiction. Pharmacology & Therapeutics. 2018, 186: 152-167.
- Al-Hasani, R.; Bruchas, R.M. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology. 2011, 115(6): 1363-81.
