Postoperative, incisional pain is the common form of acute pain. The understanding of acute pain mechanisms has advanced. This article reviews postoperative pain and proposes mechanisms for enhanced excitability of sensory neurons caused by incisions. Because effective postoperative analgesia reduces morbidity following surgery, new treatments continue to be sought. The use of regional analgesia and/or opioid via a catheter, e.g. epidural analgesia (EDA), continuous epidural infusion with patient control analgesia (CED+PCA) or patient controlled intravenous analgesia (PCIA), continuous subcutaneous infusion (+PCA) has become popular. These methods require special equipment, adequate nursing skills and professional expertise as well as the establishment of clinical procedures and an appropriate logistic setup. However, post-operative pain and cancer pain in the majority of patients is underestimated and cannot be ignored due to lack of knowledge of the proper use of basic analgesic treatment. Therefore, it makes sense to establish a standardized step-concept of postoperative pain and cancer pain management with regular quality control integrated into a multimodal program.

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Clinical studies have demonstrated that when opiates are used to control cancer pain, psychological dependence and analgesic tolerance are not a major concern. The present study was, therefore, designed to investigate the modulation of rewarding effects of morphine, fentanyl and oxycodone under inflammatory and neuropathic pain state in rodents. Rewarding effect of these opioids was evaluated by conditioned place preference paradigm. These opioids produced a significant place preference in non-inflamed and sham groups. This effect was significantly attenuated in inflamed and ligated groups as compared with the respective non-inflamed and sham groups. On the other hand, we found that the morphine-induced increase in dopamine release in the nucleus accumbens (N.Acc) was suppressed under inflammation, and the suppression was abolished by the pretreatment with κ receptor antagonist and antibody to dynorphin. These results suggest that endogenous κ-opioidergic system may be activated by chronic inflammatory nociception, resulting in the suppression of the development of rewarding effects produced by opioids. Furthermore, we demonstrated that a state of neuropathic pain induced by sciatic nerve ligation leads to the reduction in the μ-receptor function in the ventral tegmental area. This effect produces a significant decrease in the opioid-induced DA release in the N.Acc, resulting in the inhibition of rewarding effect of opioid in rats. These findings strongly indicate that treatment of opioids could be highly recommended for the relief of severe chronic pain.

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The be-all and end-all of pain control is to minimize stress induced from pain in the injured tissue. This review gives a summary account of nerve block, PCA (patient controlled analgesia) devices and pharmacologic pain management with a recent study by the palliative care team of The Jikei University School of Medicine. Recent methods for pain relief can contribute to improving the quality of life, even though it will not be the basic remedy for disease. Especially, many PCA devices and disposable pumps are available and widely used for homecare settings. When the PCA device has been activated, the pre-set analgesic dose is administered into the patient's body; and after this activation, the next dose will not be administered till a certain period of time passed. Once pain has been alleviated, no demand for pain relief until having pain return. In other words, the patient can titrate the dose of the analgesic to the safe effective dose for oneself as needed. Disposable pumps are disadvantageous in that the rescue dose cannot be changed, while the basal dose can be modified variously.

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We can use controlled-release morphine derivatives such as MS Contin, MS-Twicelon, Morphes, Kadian and P Guard in clinical situation. The former three drugs were administered twice a day and the latte two drugs were administered once a day. And we can use Oxycontin, which is controlled-release oxycodone (oxycodone is synthesized from thebaine abstracted from opium) administered twice a day. These 6 controlled-release opioids are indicated to cancer pain. When we use these controlled-release drugs we must use quick acting morphine as rescue. On the other hand, we can use controlled-release NSAIDs and prodrugs of NSAIDs. The former includes Voltaren SR Capsules and Inteban SP and the latter includes acemetacin, indomethacin farnesil, proglumetacin maleate, ampiroxicam and loxoprofen sodium.

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Fentanyl patch is a transdermal potent opioid for the treatment of chronic cancer pain. A stable serum fentanyl concentration can be maintained by dermal application every three days. In common with other opioids, fentanyl can cause adverse reactions such as constipation, nausea and vomiting. However, constipation occurred less frequently with fentanyl than with morphine. One reason for this may be fentanyl is a pure agonist and has a selective high affinity for the μ-opioid receptor. Since norfentanyl and other inactive metabolites do not contribute to the observed activity, use of this drug in geriatric patients and patients with liver/kidney dysfunction are relatively safe. Switching from lower dosage of morphine to fentanyl patch can obtain optimal analgesia more smoothly.

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Advantages and disadvantages of different routes of analgesic drug administration including rectal, oral transmucosal and intranasal routes are discussed. Although the rectal route has advantages of high bioavailability, rapid onset of action and usability by patients who cannot take medicines by mouth, some patients cannot tolerate suppositories. Transmucosal routes also have the advantages of lacking first pass effect by the liver and not having to take drugs by mouth. At present, a clinical trial is being conducted in Japan on rescue drugs by the oral transmucosal route. With the intranasal route, drug aerosol is administered into the nasal cavity and absorbed through the mucosa of the upper airway. Nebulized fentanyl has been reported. Selection of the route of administration should be made according to the patient's condition taking into consideration the advantages of each route of administration.

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To establish an in vivo method to determine nasal drug absorption and clearance from the nasal cavity, a rabbit's esophagus was cannulated with a tube, and a fluorescein/microcrystalline cellulose powder formulation was administered intranasally after recovery from anesthesia. The volumes of secreted mucus were constant during the experiment and not significantly different from those of non-administered rabbits. Fluorescein in the mucus showed a first-order clearance from the cavity. Plasma fluorescein concentration profiles of the operated group were similar to those of the control (non-operated) group. The total amount of fluorescein eliminated into the esophagus, remaining in the cavity, and absorbed from the cavity corresponded to almost 90% of the administered dose. This method allowed simultaneous determination of fluorescein absorption and clearance from the nasal cavity, which may be useful in any quantitative pharmacokinetic analysis of nasal drug delivery.

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