By Gregory Famiglio, MD
Posted on February 12, 2012 – Chronic pain is the most frequent cause of suffering and disability and is the number one reason patients seek out medical attention. Despite the attention and money spent on pain, it is a poorly understood complaint that is poorly treated by many if not most physicians. In the correctional environment, chronic pain is more likely to be ineffectively treated. Additionally, the problems of misuse, diversion and addiction make pain management in and out of prison even more challenging.
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage and can be adaptive (physiologic or acute) or maladaptive (chronic). Chronic pain implies that the injury exceeds the body’s capacity to heal or involves damage to the nervous system itself (Neuropathic Pain) creating an inability to restore physiologic function to prior homeostatic levels. For the most part, I will focus on the Neuropathic Pain Syndromes which have the common characteristic of a paradoxical coexistence of sensory deficits in the setting of painful sensation usually described as burning, electrical and/or shooting in nature and typically worse at night.
Neuropathic pain can involve the central nervous system as in stroke, traumatic spinal cord injury, demyelination (multiple sclerosis), neoplastic lesions, neuralgias, even chronic migraine and fibromyalgia or the peripheral nervous system as in nerve compression, traumatic injury, ischemia, diabetic polyneuropathy, phantom limb/stump, post herpetic neuralgia, HIV/AIDS, and chronic post surgical pain.
Wall & Melzak’s Gate Theory of Pain explains the diversity of pain perception and modulation that clinicians routinely see in the clinic. This theory involves ascending sensory tracts transmitting pain signal up to the brain, inhibitory local spinal interneurons impeding neuronal activity, and descending modulatory inhibitory control from supraspinal emotional, autonomic, memory, and cognitive regions of the brain.
In the periphery, highly repetitive stimuli of nociceptors can trigger a hyper-response of secondary neurons (wind-up) which may become sensitized and continue firing in the absence of any peripheral input. Further peripheral injury can cause spontaneous nociceptor discharge known as peripheral sensitization and may account for hyperalgesia and allodynia. Damage to the peripheral or central nervous system itself can lead to changes in the spinal cord via central sensitization, alterations in modulatory systems, and neuroplasticity (dendritic formation & sprouting in dorsal horn).
Before we move on to treatment we need to discuss the neurochemical players involved (Table 1). At least 50 different chemical are involved, but a very simplified overview follows.
Medications for Neuropathic Pain
The complex nature of neuropathic pain requires rational polypharmacy targeting multiple sites. In most studies, efficacy is considered a 30% reduction in pain.
Nonopioid analgesics (acetaminophen, NSAIDS) may help inflammatory pain if it coexists, but may have limited efficacy in neuropathic pain. Muscle relaxers have absolutely no role in true neuropathic pain.
Opioid analgesics are efficacious and versatile drugs for neuropathy for short term treatment of pain until first and second line therapies become efficacious; however, numerous systematic reviews have demonstrated that the chronic use of narcotics does not result in significant improvement in pain scores in the long term with placebo patients doing as well or better as chronic opioid patients. An exception may be with the use of methadone which is unique in its N-methyl-D-aspartate (glutamate) receptor antagonist activity and shows better long term promise and tramadol which demonstrates additional serotonin-norepinephrine reuptake inhibitor activity. The use of methadone should be limited to practitioners knowledgeable in its safe use.
Tricyclic antidepressants increase the serotonin and norepinephrine enhancing effect of the descending inhibitory pathway and generally are considered first line therapies with a Numbers Needed to Treat = 2-3. They present a long list of significant side effects however (and should never be used with duloxetine). The serotonin-norepinephrine reuptake inhibitors such as venlafaxine or duloxetine are FDA approved for diabetic peripheral neuropathy and fibromyalgia. In select patients they can be efficacious.
Antiepileptic Drugs (AEDs)
In neuropathic pain, chronic nerve injury is associated with the redistribution and altered subunit compositions of sodium and calcium channels. This predisposes neurons in sensory pathways to fire spontaneously or at inappropriately high frequencies, often from ectopic sites. AEDs may counteract this abnormal activity by selectively affecting pain-specific firing. For example, many AEDs suppress high-frequency action potentials by blocking sodium and calcium channels in a use-dependent fashion. Alternatively, AEDs may specifically target pathological channels, for example, gabapentin inhibits specific calcium channels that are overexpressed in sensory neurons after nerve injury thus reducing their spontaneous firing and perceived pain.
Post Herpetic Neuralgia
Early in post herpetic neuralgia, patients may have hyperactive or irritable nociceptors (viral inflammation) causing pain. Local anesthetic patches on for 12 hrs, then off for 12 hours has shown efficacy. Later, pain involves the loss of first-order neurons and disinhibition (spontaneous firing) of pain-conducting central pathways and may result in complete loss of skin sensation accompanied with spontaneous burning pain in the same dermatome when stroked. In refractory cases, severe pain can occur independently of any exogenous noxious stimuli. Early and even late treatment with tricyclic antidepressants (TCAs) and anticonvulsants (gabapentin, pregabalin, or valproic acid) for 90 days show efficacy here.
Diabetic Peripheral Neuropathy
The typical patient with diabetic peripheral neuropathy presents with painful feet more than legs/calves and decreased sensation and loss of deep tendon reflexes of lower extremities. The pain is described as sharp, superficial, burning or tingling, worse at rest and at night in bed, but improving with walking. It may be focal or generalized and may include autonomic neuropathies of the cardiovascular (silent ischemia, orthostasis), gastrointestinal (gastroparesis, constipation), and genitourinary (incontinence or retention) systems. Peripheral neuropathy is a late complication found in over 60% of both Type I and II diabetic patients; however, fewer than 10% complain of pain. This is thought to be the result of poor glucose control and decreased blood flow to nerves and can be improved with optimal glucose control. Tricyclic antidepressants are a good first choice to treat pain, depression and insomnia. The addition of gabapentin may give some limited improvement. Venlafaxine as both a serotonin and norepinephrine reuptake inhibitor may improve descending inhibitory modulation.
HIV and AIDS Pain
The neuropathy in HIV patients may be due to the direct neurotoxicity of HIV, opportunistic infections, or a side effect of antiviral treatment. It is most often seen in AIDS rather than HIV. Initial treatment always involves improving the viral load, treating infection and altering specific medications known to be neurotoxic. Overall, only 12% of AIDS patients will have documented distal symmetrical neuropathy and thus pain characterized by parasthesia (pins & needles), dysthesias (bad sensation), or numbness occurring in a stocking glove distribution with episodes of distal sharp, stabbing, or burning pain due to a dying back neuropathy with distal fiber loss. With the advent of HAART therapy, true distal symmetric peripheral neuropathy is becoming less common. Numerous clinical trials have repeatedly demonstrated HIV neuropathy to be refractory to most commonly assessed drugs with extremely high placebo responses found in most HIV pain trials. Although tricyclic antidepressants are considered first-line therapy and gabapentin as second-line therapy by leading experts in the field, the data shows only trace statistical significance of dubious clinical value. Most HIV inmates demand gabapentin, but few actually are helped by it.
In summary, chronic pain has many causes and has to be treated in innovative ways that alter the chronic inflammation of nociceptors, ectopic excitability of pain neurons, repair (rewire) the structural reorganization of sensory neurons in the periphery and central nervous system, and reverse the loss of descending inhibitory modulatory control which is often seen when normal sensory input is lost. Each pain experience is also a learning experience both spinally and supraspinally-a repetitive Pavlovian experience. It involves documented structural or hardware changes through actual axonal budding, synapses or nerve death as well as functional or software changes through information data flow, rerouting, altered frequencies of firing and channel density changes. Successful treatment involves reprogramming the hardware and software, altering the emotional memories, and thus the pain perception so the overall sum is holistic health. It involves pharmacotherapy, physical therapy and psychological intervention.
Dr. Famiglio is board certified as an anesthesiologist and addiction medicine specialist. He is the Medical Director at SCI-Muncy (PA DOC) and at State College Methadone Clinic, Buprenorphine Services of Centre County, and the St. Joseph Institute. Readers may contact him at gfamiglio@gmail.com.
