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Published on 1 March 2004

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Recent advances in pain management

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Anita Holdcroft
Reader in Anaesthesia and Honorary Consultant Anaesthetist
Imperial College London
Chelsea and Westminster Hospital
London
UK

Pain is recognised as a subjective symptom and, unlike many medical conditions, the patient is asked to describe and measure it. As vocabulary may be insufficient, scales and behavioural assessments have been devised to capture the multidimensional aspects of pain (see Table 1).(1) Many patients assume that pain originates from disease, since we learn at an early age that it is caused by tissue injury. However, although there may be no tissue damage, pain is still an unpleasant experience.(2) The discovery of pain memories located in the genetic control systems of nerve cells has demonstrated the potential for long-term sensitisation within the central nervous system, such that an apparently normal stimulus can generate a painful sensation.(3) Sensory abnormalities can now be measured, and strategies are used to prevent and/or reduce their occurrence.

Different strategies
One fundamental medical approach to pain management is to choose analgesic medication according to the degree of pain intensity. Using a word-descriptor scale of mild, moderate or severe in answer to the question “How much pain do you have?”, a series of step-up or -down menus can be selected as the pain increases or decreases (see Table 2). The WHO devised the step-up plan for the management of cancer pain in order to control disease progression. The step-down scheme can control postoperative pain, such that analgesics are chosen to match the degree of surgical pain. Although the simplicity of this plan is a great advantage, in cases where the experience of pain has other dimensions or when the plan does not work, alternative strategies have to be considered.(4) When these strategies are used in combination, they may relieve many different types of pain and can be tailored to individual requirements. For example, a patient with osteoarthritis may be recommended anti-inflammatory drugs, as well as graded exercise and a walking stick; alternatively, a person who has recently bruised their hand could take an analgesic for mild pain and use a cold covering and limb elevation.

Minimising the side-effects
The majority of analgesic consumption, however, is not related to such classical rationales. Over-the-counter (OTC) medications account for a substantial proportion of the analgesics sold in a multimillion-euro market. The specialty of pharmacoepidemiology has shown a number of interesting features of OTC use, especially relating to gender differences. For example, women, who have more pain disorders (of longer duration and frequency) than men, consume more analgesics even when data are adjusted for their increased experience of pain.(5) Proposed reasons for this include a greater demand for pain relief by women, which is echoed in hospital figures for attendance at pain clinics, the lack of efficacy of some available preparations (eg, mu compared with kappa opioids) in women, and the greater overall utilisation of available pain-relieving strategies by women compared with men.(6) One aspect of this analgesic use in women is the greater report of side-effects from analgesics through pharmacovigilance information. Females consistently present twice as many adverse events, compared with males. Thus, in postoperative pain management, where females use less morphine than men in patient-controlled analgesia, it has been suggested that there may be a self-imposed limitation of side-effects.

Practitioner-led methods to reduce unwanted drug effects include:

  • Combining synergistic drugs to reduce drug doses (eg, morphine and nonsteroidal anti-inflammatory drugs, codeine and paracetamol, and, neuraxially, opioids and local anaesthetics).
  • Delivering drugs directly to their site of action by appropriate techniques and formulations (eg, high- concentration capsaicin after local anaesthesia or topical opioids in a joint capsule).

A direct result of measuring drug activity and harm has been to rank analgesics according to their number-needed-to- treat (NNT) or -harm (NNH).(7) Such information is not divided into population-specific data (eg, age or disease), but it provides overall efficacy and risk information.

Long-term analgesic complications have been postulated to account for some of the presenting features in painful disorders such as irritable bowel syndrome, where constipation predominates in women compared with men. A hypothesis that needs to be tested is that constipation may be more related to gender effects in analgesic drug use than to an underlying pathology. Within the hospital community, complications from analgesic use are also observed more frequently in females; however, other interactions may have overriding importance (eg, the use of opioids in renal or hepatic failure).

Perspectives
How could pain-relieving therapies for individual patients be designed? A structured approach has been developed based on a person’s past and present pain history (including sex hormone factors and drug history), examination, diagnosis and specific pain investigations (eg, genetic background, quantitative sensory testing, nerve conduction tests and imaging).(8) Pharmacogenomics are starting to identify genetic differences in drug metabolism while, through sensory investigations, pain physicians may determine the mechanisms generating pain sensations in the nervous system. When considered together, all these factors may identify treatments specific to the mechanisms implicated in the painful sensation. For example, drugs have been developed for neuropathic pain control (eg, gabapentin, an anticonvulsant), while others possibly counteract central sensitisation (eg, ketamine, a N-methyl-D-aspartate [NMDA] antagonist); other drugs have to be fully investigated (eg, cannabinoids or nerve growth factor antagonists).

Conclusions
Past guides to pain therapies derived from classifications based on pain sites or tissue injuries are being replaced. Systematic investigations are key to designing individual analgesic combination therapies.

References

  1. Fillingim RB. Pain measurement in humans. In: Core topics in pain. London: Greenwich Medical Press; 2004. In press.
  2. Fields HL. Pain: an unpleasant topic. Pain 1999;Suppl 6: S61-9.
  3. Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002;5 Suppl 1:1062-7.
  4. Holdcroft A. Recent developments: management of pain. BMJ 2003;326:635-9.
  5. Isacson D, Bingefors K. Epidemiology of analgesic use: a gender perspective. Eur J Anaesthesiol Suppl 2002;26:5-15.
  6. Berkley KJ, Holdcroft A. Sex and gender differences in pain. In: Textbook of Pain. 4th ed. London: Churchill Livingstone; 1999. p. 951-66.
  7. McQuay H, Edwards J. Meta-analysis of single dose oral tramadol plus acetaminophen in acute postoperative pain. Eur J Anaesthesiol 2003;20 Suppl 28:19-22.
  8. Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003;102:1-8.


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