Pain is a signal triggered in the nervous system to alert us to possible injury. Acute pain, the result of sudden trauma, has a purpose. This kind of pain can usually be diagnosed and treated so the discomfort is managed and confined to a given period of time. Chronic pain, though, is much more confounding. It is the kind of alarm that doesn't go away and is resistant to most medical treatments. There may be an ongoing cause of difficult to treat pain -- arthritis, cancer, infection -- but some people have chronic pain for weeks, months and years in the absence of any obvious pathology or evidence of body damage. A type of chronic pain called neurogenic or neuropathic pain often accompanies paralysis -- it is a cruel irony for people who lack sensation to experience the agony of pain.
Pain is a complicated process that involves an intricate interplay between a number of important chemicals found naturally in the brain and spinal cord. These chemicals, called neurotransmitters, transmit nerve impulses from one cell to another.
There is a critical lack of the essential inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the injured spinal cord. This may "disinhibit" spinal neurons that are responsible for pain sensations, causing them to fire more than normal. This disinhibition is believed to be the root of spasticity, too. Recent data also suggest that there maybe a shortage of the neurotransmitter norepinephrine, as well as an over abundance of the neurotransmitter glutamate. During experiments, mice with blocked glutamate receptors show a reduction in their responses to pain. Other important receptors in pain transmission are opiate-like receptors. Morphine and other opioid drugs work by locking on to these receptors, switching on pain-inhibiting pathways or circuits, and thereby blocking pain.
Following injury, the nervous system undergoes a tremendous reorganization. The dramatic changes that occur with injury and persistent pain underscore that chronic pain should be considered a disease of the nervous system, not just prolonged acute pain or a symptom of an injury. New drugs must be developed; current medications for most chronic pain conditions are relatively ineffective and are used mostly in a trial by error manner; there are few alternatives.
The problem with chronic nerve pain is not just the distraction of hurting. Pain can lead to inactivity, which may lead to anger and frustration, to isolation, depression, sleeplessness, sadness, then to more pain. It's a spin cycle of misery with no easy exit, and modern medicine doesn't offer a wide range of help. Pain control becomes a matter of pain management; the goal is to improve function and allow people to participate in day-to-day activities.
Types of pain: Musculoskeletal or mechanical pain occurs at or above the level of spinal cord lesion and may stem from overuse of remaining functional muscles after spinal cord injury or those used for unaccustomed activity. Wheelchair propulsion and transfers are responsible for most mechanical pain.
Central pain or deafferentation pain is experienced below the level of SCI and is generally characterized by burning, aching and/or tingling. Central pain doesn't always show up right away; it may take weeks or months to appear and is often associated with recovery of some spinal cord function. This type of pain is less common in complete injuries. Other irritations, such as pressure sores or fractures, may increase the burning of central pain.
Psychological pain: Increased age, depression, stress and anxiety are associated with greater post-spinal cord injury pain. This doesn't mean the sensation of pain is in your head -- it's real, but pain appears to have an emotional component, too.
Treatment options for neuropathic pain:
Heat and massage therapy: sometimes these are effective for musculoskeletal pain related to spinal cord injury.
Acupuncture: this practice dates back 2,500 years to China and involves the application of needles to precise points on the body. While some research suggests this technique boosts levels of the body's natural painkillers (endorphins) in cerebrospinal fluid following treatment, acupuncture is not fully accepted in the medical community. Still, it is noninvasive and inexpensive compared to many other pain treatments. In some limited studies, this method helps relieve SCI pain.
Exercise: SCI patients who underwent a regular exercise program showed significant improvement in pain scores; this also accounted for improved depression scores. Even light to moderate walking or swimming can contribute to an overall sense of well-being by improving blood and oxygen flow to tense, weak muscles. Less stress equals less pain.
Hypnosis: has been shown to have a beneficial effect on SCI pain. Visual imagery therapy, which uses guided images to modify behavior helps some people alleviate pain by changing perceptions of discomfort.
Biofeedback: trains people to become aware of and to gain control over certain bodily functions, including muscle tension, heart rate and skin temperature. One can also learn to effect a change in his or her responses to pain, for example, by using relaxation techniques. With feedback and reinforcement one can consciously self-modify out-of-balance brain rhythms, which can improve body processes and brain physiology. There are many claims made for treating chronic pain with biofeedback, especially using brain wave information (EEG).
Transcranial electrical stimulation (TCES): treatment applies electrodes to an individual's scalp, allowing electrical current to be applied and presumably stimulate the underlying cerebrum. Studies indicate this newer treatment may be useful in reducing SCI-related chronic pain. Transcutaneous electrical nerve stimulation (TENS): is used for pain and has been shown to help with chronic musculoskeletal pain. In general, TENS has not been as effective for pain below injury level.
Transcranial magnetic stimulation (TMS) applies electromagnetic pulses to the brain; it has helped with post-stroke pain and in limited studies has reduced post-SCI pain over long-term use.
Spinal cord stimulation: electrodes are surgically inserted within the epidural space of the spinal cord. The patient triggers a pulse of electricity to the spinal cord using a small box-like receiver. This is most commonly used for lower back pain but some people with MS or paralysis can benefit.
Deep brain stimulation: is considered an extreme treatment and involves surgical stimulation of the brain, usually the thalamus. It is used for a limited number of conditions, including central pain syndrome, cancer pain, phantom limb pain and other types of neuropathic pain.
Magnets: are usually dismissed as pseudoscience, but proponents offer the theory that magnetic fields may effect changes in cells or body chemistry, thus producing pain relief.
Drugs: options for chronic pain include a ladder of drugs, starting with over the counter nonsteroidal anti-inflammatories such as aspirin, all the way to tightly controlled opiates such as morphine. Aspirin and ibuprofen may help with muscle and joint pain but are of minimal use for neuropathic pain. This includes COX-2 inhibitors ("superaspirins") such as celecoxib (Celebrex).
At the top of the ladder are opioids, drugs derived from the poppy plant that are among the oldest drugs known to humankind. They include codeine and the king of opiates, morphine, named for Morpheus, the god of dreams. While morphine is still the go-to therapy at the top of the treatment ladder, it is not usually a good long-term solution. It depresses breathing, causes constipation and fogs the brain. And people develop tolerance and addiction for it. Moreover, it isn't effective against many types of neuropathic pain. Scientists hope to develop a morphine-like drug that will have the pain-deadening qualities of morphine but without the drug's debilitating side effects.
There is a middle ground of medications that work for some types of chronic pain. Anticonvulsants were developed to treat seizure disorders, but are also sometimes prescribed for pain. Carbamazepine (Tegretol) is used to treat a number of painful conditions, including trigeminal neuralgia. Gabapentin (sold as Neurontin) is commonly prescribed "off label" (unapproved by the FDA) for neuropathic pain.(Pfizer, the company that owns Neurontin, pled guilty in 2004 to felonies and agreed to millions of dollars in fines for aggressive marketing of the drug for unapproved uses.)
Meanwhile, Pfizer received FDA approval in 2012 of a newer anticonvulsant to target pain, this time specific to SCI. Approval of pregabalin, marketed as Lyrica, was based on two randomized, double-blind, placebo-controlled Phase 3 trials, which enrolled 357 patients. Lyrica reduced neuropathic pain associated with SCI from baseline compared to placebo; patients receiving Lyrica showed a 30 percent to50 percent reduction in pain compared to those getting placebo. Lyrica won't work for everyone. And it comes with a wide range of possible side-effects, including anxiety, restlessness, trouble sleeping, panic attacks, anger, irritability, agitation, aggression, and a risk for suicidal behavior.
For some, tri-cyclic antidepressant drugs can be helpful for the treatment of pain. Amitriptyline (sold as Elavil and other brands) is effective in the treatment of post-SCI pain -- at least there is some evidence it works in depressed individuals.
In addition, the class of anti-anxiety drugs called benzodiazepines (Xanax, Valium) act as muscle relaxants and are sometimes used to deal with pain. Another muscle relaxant, baclofen, applied by an implanted pump (intrathecally), improves chronic post-SCI pain, but may only work when it is related to muscle spasms.
Botulinum toxin injections (Botox) which is used to treat focal spasticity, can also have an effect on pain.
Nerve blocks: employ the use of drugs, chemical agents or surgical techniques to interrupt the transmission of pain messages between specific areas of the body and the brain. Types of surgical nerve blocks include neurectomy; spinal dorsal, cranial, and trigeminal rhizotomy; and sympathetic blockade.
Physical therapy and rehabilitation: are often utilized to increase function, control pain and speed a person toward recovery.
Surgeries: for pain include rhizotomy, in which a nerve close to the spinal cord is cut, and cordotomy, where bundles of nerves within the spinal cord are severed. Cordotomy is generally used only for the pain of terminal cancer that does not respond to other therapies. The dorsal root entry zone operation, or DREZ, destroys spinal neurons corresponding to the patient's pain. This surgery can be done with electrodes that selectively damage neurons in a targeted area of the brain.
Marijuana: is illegal by federal law, but its proponents place pot alongside other pain remedies. In fact, for many years, it was sold in cigarette form by the U.S. government for just that purpose. Numerous states have partially decriminalized marijuana for medical reasons but that does not exempt users from federal prohibition laws, nor does it allow doctors to prescribe marijuana. There is medical evidence, however, to support further study; marijuana appears to bind to receptors found in many brain regions that process pain information.
Research in neuroscience will lead to a better understanding of the basic mechanisms of pain, and to more and better treatments in the years to come. Blocking or interrupting pain signals, especially when there is no apparent injury or trauma to tissue, is a key goal in the development of new medications.
National Institute of Neurological Disorders and Stroke (NINDS), National Multiple Sclerosis Society, Dana Foundation