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A Fine Line: Pain & Neurotransmitter Imbalance


Chronic pain is a persistent problem in the United States, with 30.7% of adults suffering from chronic pain – more than 50 million people. [2] Many people must deal with pain such as temporomandibular joint disorders, back pain, fibromyalgia, and neuropathy, with some people developing an incapacitating condition of chronic pain.

Opiates have been commonly prescribed to treat pain, but these drugs are no longer considered to be the top option for managing chronic pain. [12] Many people may become physically dependent on opiates and develop addictions, yet many physicians continue to prescribe them. [12] Even with opiates or other conventional methods of pain management, numerous patients endure symptoms that are not completely addressed by their current regimen. [2]

Pain is a multidimensional experience, expressed through sensory, affective, and cognitive characteristics. [16] Although the exact mechanisms behind many types of chronic pain are not yet fully understood, pain is associated with imbalances of neurotransmitters. These include inhibitory neurotransmitters serotonin and GABA, as well as excitatory neurotransmitters dopamine and norepinephrine.

Serotonin & GABA

Serotonin is intricately involved in modulating pain signaling processes. [18] Serotonin may have an inhibitory effect on pain perception; thus, low levels of serotonin may be partially responsible for pain severity. The perception, modulation, and response to pain varies between individuals. These differences are determined in part by serotonin transporter function. [8] Serotonin function is found to be deceased in people with fibromyalgia; supplementation with 5-HTP may be able to alleviate pain and other associated symptoms. Testing for serotonin levels may help identify an imbalance and guide the practitioner to appropriate therapy. [7]

GABA may enhance pain facilitation and decrease the perception of pain. [5, 11] Additionally, inhibitory GABA function is found to be reduced in neuropathy. [19]

Dopamine & Norepinephrine

Dopamine pathways influence and enhance pain processing and modulation, working to help relieve pain. [4, 17] Dopamine has important functions in controlling and reducing individuals’ perception of pain in various pain states. [16]

People with back pain have altered dopamine function; this alteration is associated with sensitivity to pain. [9] Along with back pain, the dopamine pathway is also involved in the pathophysiology of temporomandibular joint disorders, neuropathy, and other forms of chronic pain. [4]

Genetic differences affect the dopamine receptor, which may influence pain sensitivity, modulation, and susceptibility to certain kinds of pain, including neuropathy. [6] Furthermore, the presence of neuropathy can cause changes in the dopamine and serotonin systems, possibly resulting from maladaptation to chronic pain. [13] Knowing the essential role of the dopamine system in pain and analgesia can help guide treatment and assessment of risks for neuropathic pain [6]

Norepinephrine is also involved in pain; pain can cause the activation of the norepinephrine system. [10] Norepinephrine is involved in decreased sensitivity to painful stimuli (hypoalgesia) and pain relief (analgesia). [14] Norepinephrine may also increase in response to the stress of experiencing pain.

Managing Chronic Pain

There is increasing interest in incorporating complementary and alternative methods for managing chronic pain, and research has found safety and efficacy in many of these approaches. [2, 15] Some alternative therapies, such as supplementing omega-3 PUFAs, curcumin, resveratrol, theanine, and lipoic acid have been found effective for treating pain in combination with pharmaceutical drugs [1, 3]. Other interventions using CAM therapies such as mindfulness techniques, yoga, acupuncture, and qigong may help in controlling or reducing the use of opiates, and in some cases, replacing opiates. [12]

Many Americans suffer with chronic pain, often keeping them from fully participating in and enjoying their lives. Imbalances of neurotransmitters, including serotonin, GABA, dopamine, and norepinephrine, are associated with pain development, modulation, and perception. Testing individuals for deficiencies or excesses in neurotransmitter levels may reveal these imbalances, and guide the practitioner to the optimal treatment plan. A safe, effective, and individualized plan may include complementary or alternative approaches to managing chronic pain.



1. Andrea Moura, F., Queiroz de Andrade, K., Celia Farias dos Santos, J., & Oliveira Fonseca Goulart, M. (2015). Lipoic acid: Its antioxidant and anti-inflammatory role and clinical applications. Current topics in medicinal chemistry15(5), 458-483.

2. Bauer, B. A., Tilburt, J. C., Sood, A., Li, G. X., & Wang, S. H. (2016). Complementary and alternative medicine therapies for chronic pain. Chinese Journal of Integrative Medicine, 22(6), 403-411.

3. Bulaj, G., Kuhn, A., Judkins, Z. S., Ahern, M. M., Bowen, R. S., & Chen, Y. (2016). Incorporating Natural Products, Pharmaceutical Drugs, Self-care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases. Current clinical pharmacology.

4. Dawson, A., Stensson, N., Ghafouri, B., Gerdle, B., List, T., Svensson, P., & Ernberg, M. (2016). Dopamine in plasma–a biomarker for myofascial TMD pain?. The Journal of Headache and Pain17(1), 1-7.

5. Enna, S. J., & McCarson, K. E. (2006). The role of GABA in the mediation and perception of pain. Advances in pharmacology, 54, 1-27.

6. Jääskeläinen, S. K., Lindholm, P., Valmunen, T., Pesonen, U., Taiminen, T., Virtanen, A., … & Pertovaara, A. (2014). Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation. PAIN®155(10), 2180-2187.

7. Juhl, J. H. (1998). Fibromyalgia and the serotonin pathway. Alternative Medicine Review3, 367-375.

8. Kesic, M., Tvrdeic, A., Kolaric, D., Stojkovic, R., & Cicin‐Sain, L. (2015). Serotonergic modulation of pain and analgesic responses: A study in rats with constitutionally altered serotonin transporters.European Journal of Pain,19(4), 508-515.

9. Martikainen, I. K., Nuechterlein, E. B., Peciña, M., Love, T. M., Cummiford, C. M., Green, C. R., … & Zubieta, J. K. (2015). Chronic back pain is associated with alterations in dopamine neurotransmission in the ventral striatum. The Journal of Neuroscience35(27), 9957-9965.

10. Martins, I., Carvalho, P., de Vries, M. G., Teixeira-Pinto, A., Wilson, S. P., Westerink, B. H., & Tavares, I. (2015). Increased Noradrenergic Neurotransmission to a Pain Facilitatory Area of the Brain Is Implicated in Facilitation of Chronic Pain.The Journal of the American Society of Anesthesiologists,123(3), 642-653.

11. Martins, I., Carvalho, P., de Vries, M. G., Teixeira-Pinto, A., Wilson, S. P., Westerink, B. H., & Tavares, I. (2015). GABA acting on GABAB receptors located in a medullary pain facilitatory area enhances nociceptive behaviors evoked by intraplantar formalin injection. Pain156(8), 1555-

12. Mehl-Madrona, L., Mainguy, B., & Plummer, J. (2016). Integration of Complementary and Alternative Medicine Therapies into Primary-Care Pain Management for Opiate Reduction in a Rural Setting.The Journal of Alternative and Complementary Medicine,22(8), 621-626.

13. Sagheddu, C., Aroni, S., De Felice, M., Lecca, S., Luchicchi, A., Melis, M., … & Maione, S. (2015). Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain.Neuropharmacology,97, 383-393.

14. Strobel, C., Hunt, S., Sullivan, R., Sun, J., & Sah, P. (2014). Emotional regulation of pain: the role of noradrenaline in the amygdala. Science China Life Sciences57(4), 384-390.

15. Thomas, D., Maslin, B., Legler, A. et al. (2016). Role of Alternative Therapies for Chronic Pain Syndromes. Curr Pain Headache Rep 20: 29.

16. Tiemann, L., Heitmann, H., Schulz, E., Baumkötter, J., & Ploner, M. (2014). Dopamine precursor depletion influences pain affect rather than pain sensation. PloS one9(4), e96167.

17. Treister, R., Pud, D., & Eisenberg, E. (2013). The dopamine agonist apomorphine enhances conditioned pain modulation in healthy humans.Neuroscience letters548, 115-119.

18. Viguier, F., Michot, B., Hamon, M., & Bourgoin, S. (2013). Multiple roles of serotonin in pain control mechanisms—Implications of 5-HT 7 and other 5-HT receptor types.European journal of pharmacology,716(1), 8-16.

19. Yowtak, J., Wang, J., Kim, H. Y., Lu, Y., Chung, K., & Chung, J. M. (2013). Effect of antioxidant treatment on spinal GABA neurons in a neuropathic pain model in the mouse. PAIN®154(11), 2469-2476.

Clinical Contributor

[starbox id=”eharrill”]

Ramona Richard, MS, NC

Ramona Richard, MS, NC

Ramona Richard graduated with honors from the University of California with a Bachelor’s Degree in psychology and graduated summa cum laude with a Master’s Degree in Health and Nutrition Education. She also holds a Standard Designated Teaching Credential from the State of California, is a California state-certified Nutrition Consultant and a member of the National Association of Nutrition Professionals.

Ramona has participated in nutrition education in both public and private venues, including high school and college presentations, radio and public speaking for the past 20 years. She is the owner of Radiance, a nutrition consulting company, the Director of Education for Sanesco International, and a medical technical writer.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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