Chronic pain affects approximately ...

Chronic pain affects approximately 86 million Americans, substantially reducing their quality of life. (1) The socioeconomic tonnage also is significant, with chronic pain estimated to expense $90 billion annually in medical costs and reduced work productivity. (1)

Our understanding of many chronic pain disorders is evolving rapidly, and the disclosure of newer antidepressant drug classes and second-generation antiepileptic remedys has created unprecedented opportunities for the treatment of chronic pain.

Chronic and Acute Pain

Chronic and acute pain differ significantly in several important defer tos and require different treatment approaches. Acute pain is a protective answer to injury, whereas chronic pain may be a maladaptive reply Acute pain most often is nociceptive (i.e., resulting from injury or inflammation of somatic or visceral tissue). Chronic pain may be nociceptive or neuropathic (i.e., resulting from neuronal maintenance of pain either peripherally or in the central nervous regularity [CNS]).

Nociceptive pain usually is treated with anti-inflammatory or analgesic medications. Neuropathic pain typically is treated with medications that influence neurotransmitters (eg antidepressants, antiepileptic drugs) and treatment with opioids is reserv for patients with refractory neuropathic pain.

Peripheral neuropathic pain typically is described as burning, sharp, shooting, or aching, and it may be associated with tingling, dysesthesias, or numbnes Allodynia (i.e., a painful sensation from a normally nonpainful stimulus) is frequent Pain often is worse at night and may be exacerbated by means of activity.

Common non-cancer pain syndrome may be neuropathic (peripheral or central) or non-neuropathic (Table 1) (2) It is likely that the two peripheral and central mechanisms con-tribute to the persistence of mostly types of neuropathic pain. Neuropathic pain also may coexist with non-neuropathic pain (eg in about patients with chronic low back pain).

Mechanism of Action of Antidepressants and Antiepileptic put drugs intos in Pain Syndromes Transmission of painful stimuli in consequence of the spinal column and CN is modulated through excitatory and inhibitory neurotransmitters, as well as actions at sodium and calcium channels. Norepinephrine and serotonin may be excitatory or inhibitory, yet they are functionally inhibitory onward pain transmission; glutamate is the other important excitatory neurotransmitter. The chiefly important inhibitory neurotransmitter is [gamma]-aminobutyric acid (GABA). Antidepressants and antiepileptic medicines are thought to relieve neuropathic pain from one side interaction with specific neurotransmitters and ion channels (Table 2) (3)

TRICYCLIC ANTIDEPRESSANTS

Tricyclic antidepressants are conception to affect pain transmission in the spinal cord by means of inhibiting the reuptake of norepinephrine and serotonin, one as well as the other of which influence descending pain pathways. In addition, histamine [H.sub.1]-receptor affinity (associated with sedation) may be correlated with the analgesic force of antidepressants. Amitriptyline (Elavil) also has an analgesic efficiency in patients with acute pain. (4)

Tricyclic antidepressants may be categorized as secondary or tertiary amines. Secondary amines of that kind as nortriptyline (Pamelor) and desipramine (Norpramin) point out relatively selective inhibition of nor-epinephrine reuptake. Tertiary amines like as amitriptyline and imipramine (Tofranil) exhibit more balanced inhibition of norepinephrine and serotonin, if it were not that they also have greater anticholinergic side effects

The novel antidepressants venlafaxine (Effexor) and duloxetine (Cymbalta) have balanced inhibition of serotonin and norepinephrine reuptake without blockade of other neuroreceptors that are responsible for typical tricyclic side validitys The mechanism of action of bupropion (Wellbutrin) is uncertain if it be not that involves blockade of dopamine uptake.

ANTIEPILEPTIC DRUGS

Antiepileptic medicines act at several sites that may be relevant to pain, unless the precise mechanism of their analgesic purport remains unclear. These agents are deliberation to limit neuronal excitation and enhance inhibition. Relevant sites of action include voltage-gated ion channels (i.e., sodium and calcium channels), ligand-gated ion channels, the excitatory receptors for glutamate and N-methyl-D-aspartate, and the inhibitory receptors for GABA and glycine (Table 2) (3)

Antiepileptic medicines may be categorized as first or secondary generation. The second-generation agents are better tolerated, cause les sedation, and have fewer CN side effects

Clinical Efficacy

The efficacy of antidepressants and antiepi-leptic remedys varies dramatically in neuropathic and non-neuropathic pain syndrome Specific agents within each medication class can vary in effectiveness. Table 3 lists typical dosages and side forces of medications commonly used to treat chronic pain. Table 4 (4-19) reviews the flushs of evidence for these agents.

NEUROPATHIC PAIN

Antidepressants. Meta-analyses (56) have con-firmed the efficacy of tricyclic antidepressants in the treatment of neuropathic pain. Nontricyclic antidepressants point out variable degrees of efficacy in patients with neuropathic pain.