Posted by Michael Oshinsky
Program Director, Pain and Migraine, NINDS
This Pain Awareness Month blog post highlights some recent advances by NINDS-supported researchers studying pain and, more importantly, new treatments for pain sufferers. Many of these treatments are dependent on recently discovered basic science achievements in the last 10 to 15 years. As I emphasized in my Pain Awareness Month blog post last year, basic science discovery in animals is the engine for developing new treatments. Through these discoveries, innovations are achieved to alleviate pathological pain and suffering in patients. The benefit of new treatments that target novel pathways, which are highlighted here, is that they can avoid side effects such as dependence and addiction associated with chronic opioid treatment.
When most people think of treatment for pain, they think of a pill or pharmacological treatment. The experimental approaches described below transcend this idea. Through our fundamental understanding of the nervous system and molecular pathways, we are able to develop other types of treatment that are focused on the pathological changes in the brain, spinal cord, and periphery that lead to chronic pain states.
Crafted sensory input and migraine
It is well-established that migraine attacks can be exacerbated by sensory stimuli from the environment. These include light, sounds, and even light touch on the skin. Researchers supported by NINDS have been investigating the role of light sensitivity in modulating migraine pain intensity. Through this research they discovered a specific shade of green light that at low intensities actually decreases the severity of pain during a migraine attack. Migraine patients experienced increased intensity of their migraine pain in response to all shades of light tested except for this specific green wavelength. The researchers demonstrated this effect in animal models of migraine and later confirmed it in migraine patients. In other words, manipulating the environment of a patient suffering from pain can offer pain relief even in the absence of pharmacological treatment. This project gives us a window onto how crafted input from the environment might be helpful in treating neurological disorders.
Cell-based therapies for chronic pain
Researchers discovered that in patients who suffer from chronic pain, there may be a decrease in certain molecules that contribute to the health and vitality of neurons in the spinal cord that suppress pain signals. In mouse experiments, scientists found stem cells in the bone marrow that produce these needed proteins. They harvested these cells, and implanted them into the cerebrospinal fluid that surrounds the spinal cord in mouse models of chronic pain and found that there was long-term pain relief. The potential of cell-based therapies to take advantage of the body’s own redundancy and ability to heal itself opens up new possibilities for safe adaptable treatments for chronic pain sufferers.
Bioelectric medicine and pain
Our knowledge of molecular and cellular nervous system pathways and our ability to use electricity or light to control cell activity can be harnessed to modulate nerve function to treat neurological conditions. Researchers are now able to genetically manipulate cells, such that their activity can be regulated using light. Optogenetics, as this technique is called, is a biological process which involves the use of light to activate neurons that have been genetically modified to express light-sensitive ion channels. At the same time, there have been a substantial number of recent advances in our understanding of the cell types and circuitry used to process pain signals in the spinal cord. Researchers supported by NINDS have genetically modified pain-sensitive cells in the spinal cord – specifically, they have targeted cells that can inhibit pain and genetically altered them to be sensitive to light. In addition to this biological manipulation, the researchers worked with engineers to develop small flexible light-emitting diodes that can be used to apply light locally to these modified spinal cord cells in mice. This hybridization of advances in biological and electrical engineering provides new avenues for us to selectively activate or inactivate circuits in the spinal cord that carry pain signals – which could one day be used to treat pain patients with highly selective targeting of those pain circuits. The specificity of these techniques has the potential for individualized treatment for patients with a variety of chronic pain disorders.
The research landscape for chronic pain treatments is promising. There are a multitude of teams studying chronic pain and novel pharmacological and non-pharmacological treatment approaches that have low likelihood of dependence, addiction, and overdose. Research sponsored by NINDS is poised to move towards an era where physicians and patients have better options for treating chronic pain in an individualized way that will reduce patient suffering, increase quality of life, and improve function.