Options for Pain Treatment

Opioid analgesics

Pain medications may be broadly divided into two major categories: opioids and nonopioids (Table 1). Despite significant side effects, opioid analgesics remain the most potent and widely used pain-relieving drugs.(6)

These agents bind to opioid receptors where, acting as agonists, they inhibit pain-transmitting neurons and stimulate pain-inhibitory neurons. The m- and D-opioid types of receptors are most commonly associated with pain relief.(16) Opioids are typically thought of as acting centrally, but peripheral opioid receptors are present in humans. The identification of such receptors may help explain the analgesic effect of some opioids. Intra-articular morphine, for example, has a significant analgesic effect mediated through peripheral receptors.(22)

Table 1: Drugs Used in Relief of Pain

Opioid analgesics differ in their potency, speed of onset, duration of action, and route of administration. The most common side effects are sedation, respiratory depression, vomiting, enuresis, pruritus, and constipation. Although tolerance and dependence may each occur with opioid use, the risk of addiction with appropriate medical management is minimal.6 Concerns about the development of dependence on the part of patients, physicians, and pharmacists lead to underuse or suboptimal dosing of opioids in pain management.(2)

Tramadol is a centrally acting weak µ-opioid receptor agonist that also possesses nonopioid mechanisms of action. Tramadol modulates monoaminergic pathways, increasing synaptic levels of norepinephrine and serotonin in central neurons.(23) The side effects of tramadol are less severe than those of other opioids and the risk of dependence is low.(2) There are no organ-damaging risks.

Nonopioid analgesics

Aspirin and acetaminophen are two of the most widely used analgesics and are effective for mild-tomoderate headache and pain of musculoskeletal origin. Acetaminophen apparently inhibits central prostaglandin synthesis and fever but has no antiinflammatory effects. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are nonopioid analgesics that act peripherally at the site of tissue damage by blocking prostaglandin synthesis. Drugs in this class have varying degrees of anti-inflammatory, antipyretic, and analgesic properties as well as different side effects, time to onset of action, and duration of action. Aspirin, like other nonselective NSAIDs, inhibits both COX-1 and COX-2; therefore, gastrointestinal (GI) toxicity and bleeding are undesirable side effects of these analgesics. GI toxicity associated with NSAID use is substantial. Each year there are more than 100,000 NSAID-related hospitalizations, with mortality of rates of 5% to 10%.(24)

Ketorolac, a nonselective NSAID, is approved for the short-term management of moderately severe postoperative acute pain. Ketorolac has the distinction of being the only non-narcotic analgesic available in a parenteral formulation that can be administered for the relief of acute pain. Because ketorolac is nonselective, it may be contraindicated in patients with GI disorders, hypertension, renal disease, and in patients on anticoagulation therapy. Caution must be used when administering ketorolac to volume-depleted patients. All of the above conditions may complicate the perioperative state.(25)

Coxibs in acute and perioperative pain management
—Postsurgical pain is frequently undertreated.

—COX-2-selective inhibitors are effective opiate-sparing analgesic agents in the perioperative setting and are a sound addition to balanced analgesia.

—Unlike opioids and nonselective NSAIDs, COX-2-selective inhibitors do not have serious side effects (eg, bleeding) that can negatively affect surgical outcomes.

—Inhibition of COX-2-mediated prostaglandin synthesis reduces nociceptive pain and prevents inflammatory pain that leads to hyperalgesia.

—Analgesics provide more effective pain relief when used preemptively, owing to the prevention of peripheral sensitization.

—Rofecoxib has a clinically proven longer duration of action than celecoxib and nonselective NSAIDs, making it more appropriate for preemptive analgesia.

COX-2-selective inhibitors

COX-2-selective inhibitors have rapidly become an important resource for pain treatment. Rofecoxib and celecoxib are COX-2-selective inhibitors (coxibs) with anti-inflammatory, antipyretic, and analgesic properties similar to other NSAIDs and are indicated for the treatment of acute pain. Clinical data have shown that COX-2-selective inhibitors have efficacy equivalent to NSAIDs but have significantly lower risk of side effects such as GI ulceration, inhibition of platelet aggregation, or increased bleeding time.(26-28) Therefore, COX-2-selective inhibitors have potential for use in the perioperative setting.

Antidepressants and anticonvulsants

Tricyclic antidepressants may offer relief for chronic pain. Analgesic activity of tricyclic agents is initiated sooner and at a lower dose than their antidepressant activity. In addition to their effect on neurotransmitters (eg, serotonin and norepinephrine), antidepressants may potentiate opioid analgesia.(6) Tricyclic antidepressants have significant side effects. Unfortunately, newer serotonin-selective reuptake inhibitors, such as fluoxetine, lack efficacy in pain relief. Some atypical antidepressants that are more tolerable than tricyclics, such as venlafaxine and mirtazapine, are efficacious in the management of chronic pain. Anticonvulsants, such as carbamazepine, phenytoin, and the newer agent gabapentin, help relieve neuropathic pain.(6)

Topical agents

Bupivacaine and capsaicin are used topically to treat pain associated with neuralgia, neuropathy, and arthritis. Capsaicin is thought to inhibit the synthesis, transport, and release of substance P.2 Lidocaine (5%) patches may relieve postherpetic neuralgia.(29)

Other analgesic agents

Ketamine inhibits the actions of excitatory amino acids, which are thought to be critical mediators of nociception and hyperalgesia. Clonidine, a central a-receptor agonist, modulates monoamine release and has been effectively used in multimodal regimens.

Katz WA. Cyclooxygenase-2-selective inhibitors in the management of acute and perioperative pain. Cleve Clin J Med 2002;69:SI65-75.