BACKGROUND: Pain is one of the most common presenting complaints in the emergency department(ED) and adequate analgesia for painful conditions is an important goal of emergency medical practice. This study was designed to investigate on the actual condition regarding the use of analgesic injections for traumatized patients in the field of ED and to reconsider the concern and methods of pain management in the future. METHOD: We carried out a prospective, noninterventional observational clinical study of adult patients presenting with acute trauma in the ED. Using a numeric rating scale ranging from 0 to 10, patients quantified their pain intensity on arriving at the ED and on one hour after analgesic administrations in the cases of analgesic use or after initial Assessment in the cases of no analgesic use. They also were interviewed about the level of their satisfaction to pain relief before leaving the ED. RESULTS: Seventy eight percent of all patient received analgesic injections(nonsteroidal antiinflammatory drugs; 62%, opioids; 16%) and the remaining 22 patients(22%) were treated without analgesics. At the time of secondary assessment to pain, initial pain score in the cases of analgesic administration decreased. Patients who are beyond fair in the level of satisfaction were recorded for only 18% of all patient even though 78% of patients received analgesic injections. CONCLUSION: Our data illustrate that the patient of trauma commonly receive analgesic injections in the ED but their levels of satisfaction are under fair. This finding suggests that the concern and methods of pain management have to be reconsidered through the understanding of analgesic pharmacology and pattern of pain relief by analgesics.
Adult ; Analgesia ; Analgesics ; Analgesics, Opioid ; Emergencies* ; Emergency Service, Hospital* ; Humans ; Pain Management* ; Pharmacology ; Prospective Studies

The use of opioid analgesics has a long history in clinical settings, although the functions of opioid receptors, especially their role in the brain, are not well understood yet. Recent studies have generated abundant new data on opioid receptor-mediated functions and the underlying mechanisms. The most exciting finding in the past decade is probably the neuroprotection against hypoxic/ischemic stress mediated by delta-opioid receptors (DOR). An up-regulation of DOR expression and the release of endogenous opioids may increase neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers, depending on stress duration and severity, different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of ionic homeostasis, an increase in pro-survival signaling (e.g., PKC-ERK-Bcl 2) and the enhanced anti-oxidative capacity. Recent data on DOR-mediated neuroprotection provide us a new concept of neuroprotection against neurological disorders and have a potentially significant impact on the prevention and treatment of some serious neurological conditions, such as stroke.
Analgesics, Opioid ; pharmacology ; Humans ; Hypoxia ; metabolism ; Neurons ; metabolism ; Neuroprotective Agents ; pharmacology ; Receptors, Opioid, delta ; metabolism ; Signal Transduction

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
Humans ; Morphine/pharmacology* ; Hyperalgesia/metabolism* ; Analgesics, Opioid/pharmacology* ; Neurons/metabolism* ; Signal Transduction

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.
Analgesics ; Animals ; Narcotic Antagonists/pharmacology* ; Neuralgia/therapy* ; Opioid Peptides ; Rats ; Receptors, Opioid/physiology* ; Receptors, Opioid, kappa ; Spinal Cord ; Spinal Cord Stimulation

Pain is the most persistent and incapacitating symptom of recurrent or metastatic cancer. About 60~90% of patients with metastatic cancer have pain long before the terminal stage of their illness. According to a recent report, in Korea, the proportion of cancer patients who have pain is 52.1% and 62.6% of them are not given adequate analgesia. Despite widespread knowledge about many aspects of pain relief and the availability of appropriate opioid analgesics, inadequate pain management in cancer patients remains pervasive. The reasons can be classified into three categories ; societal barriers, knowledge deficits, and influenced of governmental regulations. Cancer pain can be effectively treated in 85 to 95% of patients with an integrated program of systemic, pharmacologic, and anticancer therapy. However, pain relief in cancer patients remains inadequate because it is not given priority and there is a lack of education and inappropriate understanding of the nature of cancer pain. To overcome these barriers, professional education needs to be focused on the proper assessment of pain, the management of side effects, and the use of adjuvant medications. A better understanding of the pharmacology of opioid analgesics is also needed. In addition, physicians should educate patients to report pain and to take the medications prescribed for pain management effectively.
Analgesia ; Analgesics, Opioid ; Education ; Education, Professional ; Humans ; Korea ; Pain Management ; Pharmacology ; Social Control, Formal

OBJECTIVETo observe the effects of short-term exposure to opioid analgesics on human sperm motility.

METHODSTwenty normal semen samples were collected, each divided into 19 groups, one as the control and the others treated in vitro with six opioid analgesics at three different concentrations, respectively, and sperm motility was assessed by computer-assisted sperm analysis at 15 min, 2 h and 4 h.

RESULTSCompared with the control group, fentanyl, alfentanil and sufentanil at 1 x 10(-5), 2 x 10(-3) and 0.05 mg/ml significantly decreased the percentage of grade a + b sperm at 15 min, 2 h and 4 h (P<0.05), and so did butorphanol at 2 x 10(-3) and 0.05 mg/ml (P<0.05) and dezocine at 0.05 and 0.5 mg/ml (P<0.05), but neither showed any remarkable effect at 1 x 10(-5) mg/ml at the three time points (P>0.05). Pentazocine effected no significant difference at 3 x 10(-5) and 0. 05 mg/ml (P>0.05) but a gradual increase in the percentage of grade a + b sperm at 0.5 mg/ml at the three time points (P<0.05). Butorphanol totally inhibited sperm motility at 0.05 mg/ml at 15 min and at 2 x 10(-3) mg/ml at 2 h, and so did dezocine at 0.05 and 0.5 mg/ml, but such inhibitory effect was not observed with fentanil, alfentanil and sulfentanil at 0.05 mg/ml. As for the sperm motility decreasing effect at 0.05 mg/ml at 15 min, sufentanil, butorphanol and dezocine exhibited significant differences (P<0.05) while fentanyl displayed none from alfentanil (P>0.05).

CONCLUSIONGiven the same length of time of treatment, butorphanol and dezocine totally inhibit sperm motility at a high concentration, but make no significant change at a low concentration. While fentanyl, alfentanil and sufentanil can significantly decrease sperm motility at the same low concentration, and partially inhibit it at all concentrations. On the contrary, a high concentration of pentazocine can promote human sperm motility.

Analgesics, Opioid ; pharmacology ; Humans ; In Vitro Techniques ; Male ; Sperm Motility ; drug effects

BACKGROUNDOpioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown. The µ-opioid receptor (MOR) has an important role in mediating the actions of morphine and other analgesic agents. This study is aimed at exploring the changes of MOR in the periaqueductal gray (PAG) in rats when morphine is substituted for equianalgesic fentanyl.

METHODSForty rats were randomly assigned to five treatment groups: 7 days normal saline group (N group), 7 days fentanyl group (F group), 7 days morphine group (M group), 7 days morphine and 7 days fentanyl-switching group (MF group), and 14 days morphine group (MM group). Rats repeatedly received subcutaneous injections of morphine sulfate (10 mg/kg) or equianalgesic fentanyl sulfate (0.1 mg/kg) twice daily. Rats' antinociceptive response to thermal pain was evaluated by the tail flick latency assay. MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.

RESULTSThis study showed that after morphine was substituted with fentanyl on day 8, the tail flick latency (TFL) increased from (3.9 ± 0.4) seconds to (11.4 ± 0.4) seconds. The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group (P < 0.05) but more than that in MM group (P < 0.05).

CONCLUSIONSEquianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance, which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.

Analgesics, Opioid ; pharmacology ; Animals ; Drug Tolerance ; Fentanyl ; pharmacology ; Male ; Morphine ; pharmacology ; Periaqueductal Gray ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; analysis ; genetics

AIMTo compare the antagonistic effects of 6 beta-naltrexol and naltrexone against morphine analgesia.

METHODSThe effects of 6 beta-naltrexol and naltrexone against morphine analgesia were observed in mouse heat radiant tail-flick assay and in mouse (55 +/- 1) degrees C hot plate test. The displacement of 6 beta-naltrexol and naltrexone on binding to CHO-mu receptor was observed by radioligand binding study.

RESULTS6 beta-naltrexol antagonized morphine analgesia but the potency was (6.1 +/- 1.7)% that of naltrexone. The effective duration of 6 beta-naltrexol was 3-4 times that of naltrexone and the peak time of the response was about 0.5-1 h after s.c. equivalent efficacy dose (ED95) in two models. Like naltrexone, 6 beta-naltrexol was effective by oral administration and the potency ratio of p.o./s.c. was 1/3. As an antagonist to opioid receptor, the displacement of 6 beta-naltrexol was about 12.5% that of naltrexone, which was almost in agreement with the efficacies against morphine analgesia in mouse.

CONCLUSIONCompared with naltrexone, 6 beta-naltrexol was less potent but duration was longer.

Analgesia ; Analgesics, Opioid ; antagonists & inhibitors ; Animals ; Female ; Male ; Mice ; Morphine ; antagonists & inhibitors ; Naltrexone ; analogs & derivatives ; pharmacology ; Narcotic Antagonists ; pharmacology ; Pain Threshold ; drug effects ; Receptors, Opioid, mu ; metabolism

A series of aralkyl-ketone-4-piperidol derivatives were synthesized and tested for their analgesic activities. All of the novel 30 compounds were prepared from 4-piperidone and alpha-halo-aralkyl-ketone through five steps, including Boc protection, nucleophilic addition in presence of CeCl3/NaI catalyst, deprotection, condensation and salification. Their structures were confirmed by 1H NMR and HRMS. Preliminary in vivo pharmacological trials showed that most of the synthesized compounds revealed analgesic effects. Among the tested compounds, 8, 13 and 22 exhibited potent analgesic activities in both mice writhing and mice hot plate model. The three compounds have low affinity for mu, delta, kappa receptors, which is a chance to find a better precursor of non-opioid analgesic for further optimization.
Analgesics, Non-Narcotic ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Mice ; Molecular Structure ; Pain Measurement ; Pain Threshold ; drug effects ; Piperidones ; chemical synthesis ; chemistry ; pharmacology ; Receptors, Opioid, delta ; metabolism ; Receptors, Opioid, kappa ; metabolism ; Receptors, Opioid, mu ; metabolism ; Structure-Activity Relationship

Adult ; Analgesics, Opioid ; pharmacology ; Female ; Fentanyl ; pharmacology ; Humans ; In Vitro Techniques ; Interleukin-6 ; blood ; Male ; Morphine ; pharmacology ; Narcotics ; pharmacology ; Tumor Necrosis Factor-alpha ; analysis