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Objective: The present study aimed to examine the effectiveness of intravenous administration of paracetamol added to morphine in the control of cancer pain and its possible contribution as reduction of opioid consumption and opioid-related side effects., Materials and Methods: A total of 43 patients with chronic cancer pain without neuropathic origin aged between 18 and 76 years and receiving step 2 treatment according to the World Health Organization analgesic ladder were included. Patients were randomized to receive intravenous administration of saline (control) or 1 g of paracetamol on top of morphine. Visual analog scale (VAS), patient rating index (PRI), Eastern Cooperative Oncology Group (ECOG) status, patient satisfaction, and safety were evaluated., Main Results: Both treatments resulted in improved VAS and PRI scores compared to baseline. However, groups did not differ in terms of VAS and PRI scores, morphine consumption, side-effect frequencies, laboratory values, ECOG status, and patient satisfaction., Conclusions: Although safe and there are signals for a true analgesic efficacy, our results failed to confirm any benefits of add-on treatment with intravenous administration of paracetamol. However, the study was underpowered, and future studies in this important area need to be wary of background noise and the risk of a type II error.

Purpose: To compare the efficacy, safety, and impact on daily activity of peripherally administered morphine plus a local anesthetic with that of a local anesthetic alone in patients with chronic ischemic lower extremity pain., Methods: Fifty patients with lower extremity ischemic pain due to peripheral vascular disease who had undergone surgical sympathectomy and who were not responding to systemic analgesics were included. Study treatments were bupivacaine plus morphine or bupivacaine alone administered via popliteal catheter. Each patient received both study treatments consecutively, with a washout period, in a double-blind fashion. The effects of treatments on pain severity (numerical rating scale), duration of analgesia, and daily activity were evaluated. Then, patients were asked to state which one of the treatments they preferred for the long term, during which catheter outcomes were evaluated., Results: Both treatments provided significant pain control compared to baseline at all time points, both at rest and during activity. However, the combination treatment provided superior pain control at 8 and 12 h, and longer analgesia duration (12 +/- 2 h vs 9 +/- 1 h; P < 0.001). During the long term, treatments were similar in terms of analgesia. The combination treatment had a higher incidence of side effects (30% vs 0%; P < 0.001)., Conclusion: A peripherally administered bupivacaine plus morphine combination provided better and longer analgesia for ischemic pain compared to bupivacaine alone for the short term, but not for the long term. On the other hand, our results show that continuous popliteal treatment is an effective, safe, and comfortable modality for long-term use in the home setting for patients with intractable chronic pain.

Neuropathic cancer pain represents a major challenge. Treatment often requires adjuvant analgesics, including gabapentin, to complement the effects of opioids. This study aimed to compare the effectiveness and safety of gabapentin combined with an opioid versus opioid monotherapy for the management of neuropathic cancer pain. Seventy-five cancer patients who were receiving opioid therapy and reported sufficient pain relief of nociceptive, but not neuropathic, pain were enrolled. Sixty-three patients completed the study. Patients were randomized to one of the following treatment protocols: 1) gabapentin adjuvant to ongoing opioid treatment titrated according to pain response while opioid dose was kept constant (group GO), and 2) continuation of opioid monotherapy according to the World Health Organization treatment ladder approach (group OO). Changes in pain intensity, allodynia, and analgesic drug consumption were evaluated at Day 4 and Day 13. Side effects were also recorded. Both treatments resulted in a significant reduction of pain intensity at Day 4 and Day 13 compared to baseline. However, mean pain intensity for burning and shooting pain was significantly higher in the OO group compared to the GO group at both the fourth (P=0.0001) and 13th (P=0.0001) days of the study. An earlier significant decrease (at Day 4, P=0.002) was observed for allodynia in the GO group compared to the OO group. The rate of side effects in the GO group was significantly lower than that in the OO group (P=0.015). These data suggest that gabapentin added to an opioid provides better relief of neuropathic pain in cancer patients than opioid monotherapy; this combination of gabapentin and an opioid may represent a potential first-line regimen for the management of pain in these patients.

Tramadol, a centrally acting analgesic, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+) Tramadol and the metabolite (+) -O- desmethyl-tramadol (M1) are agonists of the mu opioid receptor. (+) Tramadol also stimulates presinaptic release of serotonin and inhibits serotonin reuptake whereas (-) tramadol inhibits norepinephrine reuptake. Thus tramadol enhances inhibitory effects on pain transmission both by opioid and monoaminergic mechanisms. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. Following oral administration the bioavailability of tramadol is high and with new slow release preparations twice daily administration enables effective pain control. The recommended maximum daily dose of tramadol is 400 mg/day. Tramadol is characterised by low plasma protein binding and quite extensive tissue distribution. Elimination is primarily by the hepatic route (metabolism by CYP2D6) and partly by the renal route. It is effective in different types of moderate-to-severe acute and chronic pain, including neuropathic pain, low back pain, osteoarthritis pain and breakthrough pain. It also causes fewer opioid-type adverse effects, e.g. nausea, drowsiness, vomiting, dry mouth and constipation. Although trials in literature demonstrate immune-stimulating effects of tramadol, there are also trials suggesting immunesuppressive effects that are lesser than morphine. Owing to its pharmacological properties, tramadol is more appropriate than NSAIDs for patients suffering from gastrointestinal and renal problems. Besides its proven clinical efficacy tramadol is a safe drug as respiratory depression, cardiovascular side effects, drug abuse and dependence are of minor clinical relevance, unlike some other opioids.