Page 373 Guide to Pain Management in Low-Resource Settings

Appendix: Glossary 361

transnasal) are used depending on the clinical circum- activity in sensitized nociceptors from regenerating
stances and available substances. Local anesthetics are nerve sprouts, recruitment of previously “silent” no-
used topically and in regional (e.g., epidural) anesthetic ciceptors and Aβ fi bers, and spontaneous activity in
techniques for the treatment of acute pain (e.g., associ- dorsal root ganglion cells. Th e increase of peripheral
ated with surgery, childbirth) and some selected chronic neuronal activity is transmitted centrally and results
pain syndromes. In general, the oral route of application in sensitization of second- and third-order ascend-
is preferred, but in emergency situations and periopera- ing neurons. Among the best studied mechanisms of
tively the parenteral route is preferred. Th e use of trans- peripheral and central sensitization are the increased
dermal, oral transmucosal, and intranasal applications novel expression of sodium channels, and increased
may be benefi cial to selected patients if available, but in activity at glutamate (NMDA) receptor sites. Th e
general, high-quality pain management is possible with- mechanisms of action of antiepileptics include neuro-
out them. nal membrane stabilization by blockage of pathologi-
cally active voltage-sensitive sodium channels (carba-
Analgesics
mazepine, phenytoin, valproate, lamotrigine), blockage
Analgesics interfere with the generation and/or trans- of voltage-dependent calcium channels (gabapentin,
mission of impulses following noxious stimulation (no- lamotrigine), inhibition of presynaptic release of excit-
ciception) in the nervous system. Th is interference can atory amino acids (lamotrigine), activation of GABA
occur at peripheral and/or central levels of the neur- receptors (valproate, gabapentin), opening of K chan-
ATP
axis. Th e therapeutic aim is to diminish the perception nels (gabapentin), potential enhancement of GABA
of pain. Analgesics can be roughly discriminated by turnover/synthesis (gabapentin), increased nonvesicular
their mechanisms of action: opioids, nonsteroidal anti- GABA release (gabapentin), and inhibition of carbonic
infl ammatory drugs (NSAIDs), serotoninergic com- anhydrase in neurons (topiramate).
pounds, antiepileptics, and antidepressants. Adrenergic
Antidepressants
agonists, excitatory amino acid (e.g., N-methyl-D-aspar-
tate [NMDA]) receptor antagonists, neurokinin recep- Antidepressants are used—in the same manner as an-
tor antagonists, neurotrophin (e.g., nerve growth fac- tiepileptics—in neuropathic pain and migraine pro-
tor) antagonists, cannabinoids, and ion channel blockers phylaxis. Tricyclic antidepressants have the highest
are currently under intense investigation but are not yet eff ectivity. Th ey are titrated to eff ect. Th e purpose
used routinely. Local anesthetics are used for local and of monitoring plasma drug concentrations is not to
regional anesthetic techniques. Some drugs (e.g., trama- achieve optimal eff ect, but to avoid toxicity and con-
dol) combine various mechanisms. trol patient compliance. In most patients, pain reduc-
tion may be achieved with a low dose (e.g., 50 to 75
Antiepileptics (anticonvulsants) mg/day of imipramine or amitriptyline). As with all

Various antiepileptics (carbamazepine, phenytoin, val- coanalgesic treatment options for neuropathic pain,
proate, gabapentin, lamotrigine, and pregabalin) have patients should be told before the start of therapy that
been used for neuropathic pain and more recently for the treatment goal may only be a 50% pain reduction.
migraine prophylaxis as well. Together with antidepres- Studies have demonstrated that even with optimized
sants, they are the most eff ective coanalgesics. Th e most treatment, only half of all patients with neuropathic
common adverse eff ects are impaired mental function pain will achieve this goal. In migraine prophylaxis, the
(somnolence, dizziness, cognitive impairment, and fa- numbers are higher.
tigue) and motor function (ataxia), which may limit In patients with ischemic heart disease, there
clinical use, particularly in elderly patients. Serious side may be increased mortality from sudden arrhythmia,
eff ects have been reported, including hepatotoxicity, and in patients with recent myocardial infarction, ar-
thrombocytopenia, and life-threatening dermatological rhythmia, or cardiac decompensation, tricyclics should
and hematological reactions. Plasma drug concentra- not be used at all. Tricyclics also block histamine, cho-
tions should be monitored to avoid toxic blood levels. A linergic, and alpha-adrenergic receptor sites. Adverse
number of antiepileptics are used in neuropathic pain. events include fatigue, nausea, dry mouth, constipation,
Diff erent neuropathic pain syndromes have been attrib- dizziness, sleep disturbance, blurred vision, irritability/
uted to certain common mechanisms, including ectopic nervousness, sedation, and hepatotoxicity.