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ISSUE NO 1 7 NEWS & REVIEWS Neuropathic pain Lack of efficacy as a reason for dis- continuation of treatment seems to affect a smaller proportion of pa- tients. In some cases insufficient analgesia is due to an incorrect diag- nosis of the type of pain or the use of an incorrect drug or dose. Where pain has a neuropathic component, the analgesic potency of opioids can be limited by patho- physiological mechanisms; opioid receptors are down regulated and central neurotransmitters are released, reducing opioid responsiveness and producing relative opioid tolerance (Davis 2007)3. Although there is evidence that neuropathic pain does respond to opioids (Ballantyne 2008)4, higher doses may be required than for treatment of nociceptive pain, and these may initiate the Vicious Circle. Because effective treatment of this type of pain requires more than one mechanism of action, the combination of analgesics with other agents such as anti-convulsants and anti- depressants is frequently used. However, combination therapy increases the risk of side effects and the possibility of drug-drug interactions. Interactions Pharmacological drug-drug inter- action which reduces the serum concentration of active analgesic substances can result in insufficient analgesia. It also has the potential to increase side effects, again leading to low compliance and ineffective treat- ment. Besides, many patients have problems complying with the amount of medication they need to take.This high “pill burden” is a source of dis- satisfaction for many patients and can also lead to non-compliance. COMMENTARY Professor Joseph Pergolizzi, of the Johns Hopkins University School of Medicine discusses the difficulties in balancing pain relief and tolerability Achieving optimal analgesia for patients suffer- ing from severe chronic pain can be difficult, es- pecially if a neuropathic component exists. Three main reasons for this are the lack of efficacy, tolerance with the drug, and issues of tolerability. All three can create a Vicious Circle that can limit the effectiveness of pharmacological management strategies. A clear understanding of these issues is essential in order to optimise our management of chronic pain. Therefore, we need to re-evaluate our approach to the treatment and management of severe chronic pain. experience at least one adverse event, with gastrointestinal (GI) and CNS side effects being the most common. Nausea and vomiting can be highly distressing to the patient and constipation can impose a substantial impact on quality of life. CNS side effects such as somnolence and dizziness are also common side effects likely to lead to reduced treatment success. Conclusion Overall, physicians and patients are often struggling to find a balance between sufficient analgesia and acceptable tolerability, indicating that current treatment of severe chronic pain often remains inefficient. Tolerance Analgesic tolerance development is another condition which may affect chronic pain patients taking opioids. This occurs when a constant dose of a substance loses its analgesic effect over time. Besides the option to switch to another opioid, the nor- mal response to this situation is to increase drug dose. Often at the same time the drug’s potential to evoke side effects will be increased, so that the Vicious Circle will start again. These factors will all affect reliability and stability of treatment. Adverse events However, adverse events are found to be the main reason for treatment discontinuation in about one out of four patients taking opioids (Moore and McQuay, 20051 ; Kalso, 20042 ). Evidence from reviews of clinical trials have indicated that at least half of the patients taking opioids References 1. Moore R, McQuay H 2005. (See abstract on p.8) 2. Kalso E et al. 2004. (See abstract on page 8) 3. Davis MP.What is new in neuropathic pain? Support Care Cancer. 2007; 15(4): 363-372. 4. Ballantyne JC, Shin N. Efficacy of opioids for chronic pain. A review of the evidence. Clin J Pain 2008; 24(6):469-78.