Mechanism orientated pharmacological treatment

The mechanisms underlying chronic pain can be multifactorial and reflect a variety of physiological changes in pain signalling and perception. Chronic pain often comprises a nociceptive and a neuropathic element, among others. Examples of chronic pain that is multifactorial in nature include chronic back pain and cancer pain involving bone metastases and nerve infiltration.1-2

Chronic pain is seldom controlled by the use of a single type of analgesic agent and instead, a combination of drugs, acting via different mechanisms, often is employed.3-6

The rationale for combining drugs with differing modes of action is that together these agents target the multiple mechanisms at play in complex chronic pain conditions, addressing both nociceptive and neuropathic components of pain.

By combining agents it is possible to achieve a degree of synergy between drugs such that a greater analgesic effect is achieved. For example, although opioids offer potent analgesic activity against nociceptive components of pain, their effectiveness against neuropathic pain is less, such that higher drug doses would be required for analgesia. However, the combination of an opioid with an antidepressant or anticonvulsant agent offers activity against neuropathic pain components, and may achieve a level of pain relief in complex chronic pain conditions that neither agent could deliver alone.

The use of agents with more than one mode of action (MoA) offers the potential for synergistic analgesia.3-6, 8

Treatment goals for chronic pain need to be individualized and agreed upon by patient and physician.7 Goals need to include reduction in pain and changes in the pain experience. This is best achieved through a combination of coping strategies and use of treatments that target the presumed underlying mechanism of pain. Therapeutic aims consensus must be individualized and should consider not just reverting and preventing pain chronification but also restoration of the normal processes of pain control and modulation.

Goals of treatment include reduction of pain, change in pain experience, improvement in quality of life, and allowing patients improved function at all levels – work, physical, and social.7


1 Baron R, Binder A. Orthopade. 2004;33:568-75.
2 Banning A, et al. Pain. 1991;45:45-8.
3 Varrassi G et al. Pharmacological treatment of chronic pain – the need for CHANGE. Curr Med Res Opin. 2010; 26(5):1231-1245.
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5 Raffa R. Clin Rheumatol. 2006;25:S9-15.
6 Gottschalk A. et al. New concepts in acute pain therapy: preemtive analgesia. Am Fam Physician. 2001; 63:1979-84.
7 Clark TS. Interdisciplinary treatment for chronic pain: Is it worth the money? Proc (Bayl Univ Med Cent). 2000; 13:240-3.
8 Kehlet H et al. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg. 1993; 77:1048-56.