Hyperalgesia: An Emerging Iatrogenic Syndrome

Anesthesia and Intensive Care Unit & Pain Relief and Palliative Care Unit, La Maddalena Cancer Center, Palermo, Italy.
Journal of Pain and Symptom Management (Impact Factor: 2.8). 09/2003; 26(2):769-75. DOI: 10.1016/S0885-3924(03)00258-6
Source: PubMed


Clinical reports suggest that opioids, intended to abolish pain, can unexpectedly produce hyperalgesia. This paradoxical effect may be mechanistically related to tolerance induced by increasing doses of opioids. Two case reports illustrate a syndrome characterized by increasing pain pursued by escalating opioid doses, which results in a worsening of the clinical picture. Several experimental data may help explain the course of this challenging clinical condition. In escalating opioid doses rapidly, a risk of opioid-induced hyperalgesia should be recognized, as higher doses of opioids may stimulate rather than inhibit the central nervous system by different mechanisms. Alternative procedures should be taken into consideration to break this cycle, should it occur. More data are needed to detect this condition, as currently no diagnostic information on specific markers, clinical or biochemical, exists.

Download full-text


Available from: Sebastiano Mercadante
  • Source
    • "Furthermore, Chen and pan found that blockade expression of TRPV1 in the dorsal root ganglion (DRG) increases the analgesic effects of opioids.7 TRPV1, therefore, seems to have an antagonist effect on opioids. On the other hand, it has been documented that excessive and chronic administration of opioids can lead to increased pain;8 knock out TRPV1 mice do not develop this pain increase.9 It may be concluded that TRPV1 channels also play an important role in increased pain following chronic administration of opioids. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Chronic use of opioids usually results in physical dependence. The underlying mechanisms for this dependence are still being evaluated. Transient receptor potential vanilloid type 1 (TRPV1) are important receptors of pain perception. Their role during opioid dependence has not been studied well. The aim of this study was to evaluate the effect of morphine-dependence on the expression of TRPV1 receptors in the amygdala and CA1 region of the hippocampus. Methods: This study used four groups of rats. Two groups of rats (morphine and morphine+naloxone) received morphine based on the following protocol: 10 mg/kg (twice daily, 3 days) followed by 20, 30, 40 and 50 mg/kg (twice daily), respectively, for 4 consecutive days. Another group received vehicle (1 ml/kg) instead of morphine given using the same schedule. The morphine+naloxone group of rats additionally received naloxone (5 mg/kg) at the end of the protocol. The control group rats received no injections or intervention. The amygdala and CA1 regions of the morphine, saline-treated and intact animals were isolated and prepared for real-time PCR analysis. Results: Administration of naloxone induced withdrawal signs in morphine-treated animals. The results showed a significant decrease in TRPV1 gene expression in the amygdala (P<0.05) but not the CA1 region of morphine dependent rats. Conclusion: TRPV1 receptors may be involved in morphine-induced dependence.
    Full-text · Article · May 2014 · Iranian Journal of Medical Sciences
  • Source
    • "This is a rare effect and has not been known for a long time, so it is understandable that many pharmacists are indeed unaware of this adverse effect. However, the clinical effects can be significant if the dose of opioids is increased instead of decreased when a patient suffers from opioid-induced pain sensitivity [11, 40, 41]. Although the majority of the pharmacists stated that life-threatening respiratory depression represent no real danger to the use of opioids for pain control [35], 25% thought it was a real danger. "
    [Show abstract] [Hide abstract]
    ABSTRACT: What is the level of knowledge of pharmacists concerning pain management and the use of opioids at the end of life, and how do they cooperate with physicians? A written questionnaire was sent to a sample of community and hospital pharmacists in the Netherlands. The questionnaire was completed by 182 pharmacists (response rate 45%). Pharmacists were aware of the most basic knowledge about opioids. Among the respondents, 29% erroneously thought that life-threatening respiratory depression was a danger with pain control, and 38% erroneously believed that opioids were the preferred drug for palliative sedation. One in three responding pharmacists did not think his/her theoretical knowledge was sufficient to provide advice on pain control. Most pharmacists had working agreements with physicians on euthanasia (81%), but fewer had working agreements on palliative sedation (46%) or opioid therapy (25%). Based on the experience of most of responding pharmacists (93%), physicians were open to unsolicited advice on opioid prescriptions. The majority of community pharmacists (94%) checked opioid prescriptions most often only after dispensing, while it was not a common practice among the majority of hospital pharmacists (68%) to check prescriptions at all. Although the basic knowledge of most pharmacists was adequate, based on the responses to the questionnaire, there seems to be a lack of knowledge in several areas, which may hamper pharmacists in improving the quality of care when giving advice to physicians and preventing or correcting mistakes if necessary. If education is improved, a more active role of the pharmacist may improve the quality of end-of-life pharmacotherapy.
    Full-text · Article · Jan 2011 · European Journal of Clinical Pharmacology
  • Source
    • "E.g. less than one in three physicians was aware that opioids may cause or worsen pain. Although this is a rare effect the clinical effects can be significant if the dose of opioids is increased instead of decreased when a patient suffers from opioid-induced pain sensitivity [39-42]. There also seemed to be a lack of awareness that decreased renal function raises plasma concentration of morphine(-metabolites). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pain is still one of the most frequently occurring symptoms at the end of life, although it can be treated satisfactorily in most cases if the physician has adequate knowledge. In the Netherlands, almost 60% of the patients with non-acute illnesses die at home where end of life care is coordinated by the general practitioner (GP); about 30% die in hospitals (cared for by clinical specialists), and about 10% in nursing homes (cared for by elderly care physicians).The research question of this study is: what is the level of knowledge of Dutch physicians concerning pain management and the use of opioids at the end of life? A written questionnaire was sent to a random sample of physicians of specialties most often involved in end of life care in the Netherlands. The questionnaire was completed by 406 physicians, response rate 41%. Almost all physicians were aware of the most basal knowledge about opioids, e.g. that it is important for treatment purposes to distinguish nociceptive from neuropathic pain (97%). Approximately half of the physicians (46%) did not know that decreased renal function raises plasma concentration of morphine(-metabolites) and 34% of the clinical specialists erroneously thought opioids are the favoured drug for palliative sedation.Although 91% knew that opioids titrated against pain do not shorten life, 10% sometimes or often gave higher dosages than needed with the explicit aim to hasten death. About half felt sometimes or often pressured by relatives to hasten death by increasing opioiddosage.The large majority (83%) of physicians was interested in additional education about subjects related to the end of life, the most popular subject was opioid rotation (46%). Although the basic knowledge of physicians was adequate, there seemed to be a lack of knowledge in several areas, which can be a barrier for good pain management at the end of life. From this study four areas emerge, in which it seems likely that an improvement can improve the quality of pain management at the end of life for many patients in the Netherlands: 1)palliative sedation; 2)expected effect of opioids on survival; and 3) opioid rotation.
    Full-text · Article · Nov 2010 · BMC Palliative Care
Show more