Adjuvant Analgesia for Management of Chronic Pain
To date, clinical pain practice relies on opioids as the primary analgesics for the management of moderate to severe pain. Adjuvant analgesics use has become increasingly important especially in the management of mild to moderatepain. Adjuvants act on either the excitatory (e.g., substance P, and glutamate), inhibitory neurotransmitters (e.g., GABA), or on neurotransmitters that modulate pain experience (e.g., serotonin, norepinephrine).
Traditional Adjuvant Analgesics
Traditional adjuvant analgesics such as the NSAIDs, acetaminophen, and muscle relaxants will be briefly described first before discussing the newer adjuvants.
- NSAIDs and Acetaminophen. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used. It is important to note that Acetaminophen is not an anti-inflammatory medication. Along with mild narcotics, NSAIDs remain the mainstay of treating mild pain. They are usually well tolerated and are often used to address inflammatory processes, such as muscle aches, strains, or sprains. NSAIDs, as a class, have analgesic, antipyretic, and anti-inflammatory effects although not all of them are FDA-approved for analgesia use. They have the advantage of a very low short-term side-effect profile that does not impact the patient’s lifestyle. They are called non-steroidal because no steroid agent is present in them. Aspirin, for decades now, remains the prototypical agent. Other examples include ibuprofen (Advil, Motrin), naproxen (Naprosyn), and indomethacin (Indocin). NSAIDs can be used synergistically with opioids and for pain not responsive to opioids alone–especially in patients with bone pain and incidental pain. Unlike opioids, NSAIDs do not cause ileus or sedation. Acetaminophen is recommended by the American Geriatrics Society (AGS) as the drug of choice for mild to moderate musculoskeletal pain. It has an excellent safety profile at therapeutic doses that can be up to 4000 mg/day. Toradol (Ketorolac) is an injectable NSAID that is a potent analgesic (30 mg is roughly equivalent to 7-10 mg of morphine) but has the potential for gastric irritation and possible bleeding.1
- COX-2 Inhibitors.Celecoxib (Celebrex) and rofecoxib (Vioxx) mainly inhibit the enzyme cyclo-oxygenase-2 (COX-2) and thereby result in anti-inflammatory effects with no, or much less, gastric and renal side effects. They reportedly have fewer drug interactions and have no effect on platelet aggregation or bleeding time commonly found with traditional NSAIDs. COX-2 inhibitors are not free of side effects and package inserts should be read thoroughly before prescribing these drugs. Both rofecoxib and valdecoxib (Bextra) have been taken off the market because of concerns of potential side effects. Meloxicam (Mobic) is not a typical COX-2 inhibitor although some have called for re-classifying it as such.
- Muscle Relaxants. Skeletal muscle relaxants are used to ‘relax muscles,’ relieve stiffness, and decrease pain and discomfort caused by strains, sprains, or other injury to muscles or joints. However, they do not take the place of rest, exercise, physical therapy, or other modalities. Commonly used drugs in this class include: baclofen (Lioresal), carisoprodol (Soma), cyclobenzaprine (Flexeril), diazepam (Valium), methocarbamol (Robaxin), orphenadine (Norflex), metaxalone (Skelaxin), and tizanidine (Zanaflex). They all act on the central nervous system (CNS) to produce their depressant effect. It is important to note that, since muscle relaxants act centrally, they indiscriminately relax all muscles and leave the injured area exposed to reinjury if used for long term. It is strongly recommended they be used for a short-term basis only. Note that sudden cessation of the use of baclofen has been associated with withdrawal symptoms and signs.
Tizanidine (Zanaflex) is a centrally acting agent and also is an alpha2-adrenergic agonistic that may contribute some analgesic properties. It is used for acute low back pain, acute musculoskeletal neck pain, and chronic tension headache. This agent has a reversible liver toxicity and should be used with caution. Cari-sporodol (Soma) is a popular muscle relaxant with an active byproduct metabolite, meprobamate—a barbiturate—that is potentially addictive. The use of alprazolam (Xanax) as a muscle relaxant is not clinically warranted.
Psychotropic drugs have increasingly been used in the management of chronic pain. The value of psychotropic medications lie in their capacity to modulate pain experience and to treat symptoms which trigger, exacerbate, or compound the effects of pain—notably depression, anxiety, sleep disturbance, anger, and other states of neural excitation. Classes of psychotropic medications commonly used in pain management include: antidepressants (ADs) and anti-epileptic drugs (AEDs). Other psychotropic drugs that are used clinically include anti-anxiety agents, stimulants, and major tranquilizers.