Opioid-induced hyperalgesia

Recently it became clear that opioids, besides their role in analgesia, mayalso induce hyperalgesia. Something what in the past was called opioidneurotoxicity. Hyperalgesia, or hypersensitivity to pain stimuli may berelated to well known problems of tolerance to opioids. Hyperalgesia is amajor clinical problem and its recognition and treatment are of paramountimportance. It is believed that uncoupling of opioid receptors from theGi/Go proteins and coupling them to Gs protein changes dramatically activityof opioid receptors. In this article the different aspects of diagnosis andtreatment of hyperalgesia are discussed.Recently it became clear that opioids, besides their role in analgesia, mayalso induce hyperalgesia. Something what in the past was called opioidneurotoxicity. Hyperalgesia, or hypersensitivity to pain stimuli may berelated to well known problems of tolerance to opioids. Hyperalgesia is amajor clinical problem and its recognition and treatment are of paramountimportance. It is believed that uncoupling of opioid receptors from theGi/Go proteins and coupling them to Gs protein changes dramatically activityof opioid receptors. In this article the different aspects of diagnosis andtreatment of hyperalgesia are discussed

The pain, the oncologist

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Is there enough evidence to advocate opioid combinations? Does one and one make two or more?

Despite a more than tenfold increase in opioid consumption in the past decades, many cancer patients still suffer pain. The current understanding of this situation is poorly understood. It is still possible that in some countries pain is still undertreated, but it is also possible that we do not appreciate opioid induced toxicity and other phenomena an/or our opioid prescribing needs to be refreshed. At the moment the only evidence based tool to deal with opioid toxicity is switching to another opioid. Other methods are also described, but are far less well evidenced. However, the effects after switching are short-lived and sometimes a number of switches are needed. In this article we discuss the rationale behind and the possibility of combining different opioids with each other. Opioids are all different and opioid receptors are heterogenous. There are data to suggest that widening the activity spectrum of opioids may be the way forward in order to decrease adverse effects and maintain analgesia. At the moment there are only some data on the interaction of fentanyl and morphine, morphine and oxycodone, and buprenorphine and morphine. These data suggest that we should investigate these problems vigorously and, instead of switching from one opioid to another, we may, in future, adopt the concept of a semi-switch, where the dose of the first opioid is decreased and a second opioid is added. Adv. Pall. Med. 2010; 9, 2: 31–38Despite a more than tenfold increase in opioid consumption in the past decades, many cancer patients still suffer pain. The current understanding of this situation is poorly understood. It is still possible that in some countries pain is still undertreated, but it is also possible that we do not appreciate opioid induced toxicity and other phenomena an/or our opioid prescribing needs to be refreshed. At the moment the only evidence based tool to deal with opioid toxicity is switching to another opioid. Other methods are also described, but are far less well evidenced. However, the effects after switching are short-lived and sometimes a number of switches are needed. In this article we discuss the rationale behind and the possibility of combining different opioids with each other. Opioids are all different and opioid receptors are heterogenous. There are data to suggest that widening the activity spectrum of opioids may be the way forward in order to decrease adverse effects and maintain analgesia. At the moment there are only some data on the interaction of fentanyl and morphine, morphine and oxycodone, and buprenorphine and morphine. These data suggest that we should investigate these problems vigorously and, instead of switching from one opioid to another, we may, in future, adopt the concept of a semi-switch, where the dose of the first opioid is decreased and a second opioid is added. Adv. Pall. Med. 2010; 9, 2: 31–3

Insomnia in patients with advanced lung cancer admitted to palliative care services.

Aim To assess the prevalence of insomnia and possible associated factors in patients with advanced lung cancer admitted to different settings of palliative care. Methods Secondary analysis of a consecutive sample of patients with advanced lung cancer receiving palliative care. Epidemiological and clinical data, treatments received in the last month, Karnofsky status, Edmonton Symptom Assessment System (ESAS), Athens Insomnia Scale (AIS) and the Hospital Anxiety and depression scale (HADS), as well as concomitant medical treatment were recorded. Results One-hundred-eight-two patients with advanced lung cancer were surveyed. The mean age was 69.9 years (SD 10.8), and 121 patients (66%) were men. The majority of patients showed consistent levels of insomnia. A poor Karnofsky level, pain, nausea, and drowsiness, time from diagnosis (1-3 years), HADS anxiety, and HADS depression, were positively associated with insomnia. Conclusions About 50% of patients with advanced lung cancer admitted to palliative care services had relevant insomnia. Several factors associated with insomnia have been identified and should prompt physicians for a careful examination and subsequent treatment

Intranasal fentanyl versus fentanyl pectin nasal spray for the management of breakthrough cancer pain in doses proportional to basal opioid regimen.

Abstract The aim of this randomized, crossover, comparison study was to assess the analgesic and adverse effects of 2 nasal preparations, intranasal fentanyl (INFS) and fentanyl pectin nasal spray (FPNS), for breakthrough pain, given in doses proportional to opioid basal regimen. Each patient randomly received INFS or FPNS in doses proportional to opioid dosages used for background analgesia for 2 pairs of episodes. For each episode of breakthrough pain, pain intensity and adverse effects intensity were recorded just before starting the INFS or FPNS (T0) and 5 minutes (T5), 10 minutes (T10), and 20 minutes (T20) after the administration of the nasal drugs. Sixty-nine patients were studied. The mean age was 63.4 years, and 37 patients were males. For the present analysis, 188 episodes were considered. A statistical decrease in pain intensity was observed with both nasal drugs after 5, 10, and 20 minutes. A decrease in pain intensity of >33% was observed in 16, 102, and 159 treated episodes at T5, T10, and T20, respectively. Adverse effects were of mild nature in most cases or were preexistent because of basal opioid therapy. No differences were found in summed pain intensity difference 20 minutes after dosing. Most of patients did not find substantial preferences. INFS and FPNS were effective and well-tolerated treatments for breakthrough pain management. Both delivery systems, in doses proportional to the basal opioid regimen, provided significant analgesia within 10 minutes, without producing relevant adverse effects. PERSPECTIVE: This article showed that INFS and FPNS in doses proportional to basal opioid regimen are equally safe and effective for the management of breakthrough pain in cancer patients. These data provide new insights on the use of nasal preparations of fentanyl

Czy jest wystarczająco dużo dowodów, aby zalecać kojarzone stosowanie opioidów? Czy jeden plus jeden tworzy dwa czy może więcej?

Mimo ponad 10-krotnego wzrostu zużycia opioidów w ostatnich dekadach, nadal wielu pacjentów z chorobą nowotworową cierpi z powodu bólu. Obecny stan wiedzy w tej dziedzinie jest jeszcze niezadowalający. Z jednej strony, ból jest wciąż niedostatecznie leczony, jak to ma miejsce w niektórych krajach, a z drugiej, "zapomina się" o toksyczności opioidów, stosując zbyt wysokie dawki. W związku z tym należy zaktualizować wiedzę dotyczącą leków opioidowych. Obecnie jedyną udowodnioną metodą zmniejszenia toksyczności opioidów jest ich rotacja (inne metody są znacznie mniej zbadane). Niestety, pozytywne skutki zamiany jednego środka na drugi są krótkotrwałe i czasem rotacji leków należy dokonywać kilkukrotnie. W niniejszym artykule omówiono zasadność oraz możliwość stosowania kombinacji różnych opioidów. Leki te różnią się od siebie, a ich receptory wykazują heterogenność. Wiele danych wskazuje na to, że poszerzenie spektrum działania opioidów poprzez ich skojarzenie może prowadzić do zmniejszenia ryzyka działań niepożądanych, przy utrzymaniu efektu przeciwbólowego. Obecnie są znane tylko badania dotyczące łączenia fentanylu z morfiną, morfiny z oksykodonem oraz buprenorfiny z morfiną. Z uzyskanych danych wynika, że w przyszłości leczenie powinno się opierać na koncepcji niepełnej rotacji, której celem jest obniżenie dawki pierwszego opioidu i dodanie drugiego, a całkowitą zamianę jednego leku na drugi należy zastąpić tą nową metodą. Medycyna Paliatywna w Praktyce 2010; 4, 3: 111-11

Pain Catastrophizing in Cancer Patients

Simple Summary Catastrophism was not associated with the levels of pain intensity, PSG, PSGR, and PGI for pain, except the rumination subscale that was independently associated with pain intensity at T0. A comprehensive palliative care management provided the relevant changes in symptom burden and annulled the pain expression associated with rumination.Abstract Background: Pain catastrophizing is a group of negative irrational cognitions in the context of anticipated or actual pain. The aim of this study was to decipher the possible role of catastrophism on pain expression and outcomes after a comprehensive palliative care treatment. Methods: A consecutive sample of patients with uncontrolled pain was assessed. Demographic characteristics, symptom intensity included in the Edmonton symptom assessment system (ESAS), and opioid drugs used were recorded at admission (T0). The Pain Catastrophizing Scale (PCS) was measured for patients. Patients were also asked about their personalized symptom goal (PSG) for each symptom of ESAS. One week after a comprehensive palliative care treatment (T7), ESAS and opioid doses used were recorded again, and the number of patients who achieved their PSG (PSGR) were calculated. At the same interval (T7), Minimal Clinically Important Difference (MCID) was calculated using patient global impression (PGI). Results: Ninety-five patients were eligible. A significant decrease in symptom intensity was reported for all ESAS items. PGI was positive for all symptoms, with higher values for pain, poor well-being, and poor sleep. Only the rumination subscale of catastrophism was significantly associated with pain at T0 (B = 0.540; p = 0.034). Conclusions: Catastrophism was not associated with the levels of pain intensity, PSG, PSGR, and PGI for pain, except the rumination subscale that was associated with pain intensity at T0. A comprehensive palliative care management provided the relevant changes in symptom burden, undoing the pain expression associated with rumination

Breakthrough Cancer Pain in Patients With Abdominal Visceral Cancer Pain

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Methadone versus morphine for postoperative pain in patients undergoing surgery for gynecological cancer: A randomized controlled clinical trial

The aim of this study was to compare methadone and morphine for the management of postoperative

Methadone as First-line Opioid for the Management of Cancer Pain

Aim The aim of this study was to assess the efficacy and adverse effects of methadone when used as first-line therapy in patients that are either receiving low doses of opioids or none. Methods Patients with advanced cancer were prospectively assessed. Opioid-naive patients (L-group) were started with methadone at 6 mg/day. Patients receiving weak or other opioids in doses of <60 mg/day of OME (H-group) were started with methadone at 9 mg/day. Methadone doses were changed according to the clinical needs to obtain the most favorable balance between analgesia and adverse effects. Edmonton Symptom Asssement Score (ESAS), Memorial Delirium Assessment Score (MDAS), doses of methadone, and the use of adjuvant drugs were recorded before starting the study treatment (T0), 1 week after (T7), 2 weeks after (T14), 1 month after (T30), and 2 months after (T60). Methadone escalation index percent (MEI%) and in mg (MEImg) were calculated at T30 and T60. Results Eighty-two patients were assessed. In both groups H and L, there were significant changes in pain and symptom intensity at the different times during the study. Adverse effects as causes of drop-out were minimal. Mean MEImg was 0.09 (SD 0.28) and 0.02 (SD 0.07) at T30 and T60, respectively. MEI% was 1.01 (SD 3.08) and 0.27 (SD 0.86) at T30 and T60, respectively. Conclusion Methadone used as a first-line opioid therapy provided good analgesia with limited adverse effects and a minimal opioid-induced tolerance