BACKGROUND: Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals. OBJECTIVE: To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output. MAIN OUTCOME MEASURES: The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA. RESULTS: Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05). CONCLUSION: Low-level LA gradually reduced older patients' postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care. TRIAL REGISTRATION ClinicalTrials.gov registration number NCT03995446.
Acupuncture Therapy ; Aged ; Analgesics, Opioid/therapeutic use* ; Arthroplasty, Replacement, Knee/adverse effects* ; Double-Blind Method ; Humans ; Morphine/therapeutic use* ; Pain, Postoperative/drug therapy* ; Single-Blind Method

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.
Anesthetics, Local/therapeutic use* ; Double-Blind Method ; Hepatectomy/adverse effects* ; Humans ; Morphine/therapeutic use* ; Pain Measurement ; Pain, Postoperative/etiology* ; Ultrasonography, Interventional

BACKGROUND: Neuropathic pain, including paresthesia/dysesthesia in the lower extremities, always develops and remains for at least one month, to variable degrees, after percutaneous endoscopic lumbar discectomy (PELD). The recently discovered dual analgesic mechanisms of action, similar to those of antidepressants and anticonvulsants, enable nefopam (NFP) to treat neuropathic pain. This study was performed to determine whether NFP might reduce the neuropathic pain component of postoperative pain. METHODS: Eighty patients, who underwent PELD due to herniated nucleus pulposus (HNP) at L4-L5, were randomly divided into two equal groups, one receiving NFP (with a mixture of morphine and ketorolac) and the other normal saline (NS) with the same mixture. The number of bolus infusions and the infused volume for 3 days were compared in both groups. The adverse reactions (ADRs) in both groups were recorded and compared. The neuropathic pain symptom inventory (NPSI) score was compared in both groups on postoperative days 1, 3, 7, 30, 60, and 90. RESULTS: The mean attempted number of bolus infusions, and effective infused bolus volume for 3 days was lower in the NFP group for 3 days. The most commonly reported ADRs were nausea, dizziness, and somnolence, in order of frequency in the NFP group. The median NPSI score, and all 5 median sub-scores in the NFP group, were significantly lower than that of the NS group until postoperative day 30. CONCLUSIONS: NFP significantly reduced the neuropathic pain component, including paresthesia/dysesthesia until 1 month after PELD. The common ADRs were nausea, dizziness, somnolence, and ataxia.
Anticonvulsants ; Antidepressive Agents ; Ataxia ; Diskectomy* ; Diskectomy, Percutaneous ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Infusions, Intravenous ; Intervertebral Disc Displacement ; Lower Extremity ; Morphine ; Nausea ; Nefopam* ; Neuralgia ; Pain, Postoperative ; Paresthesia* ; Symptom Assessment

Amygdala ; drug effects ; metabolism ; Animals ; Conditioning (Psychology) ; Morphine ; adverse effects ; Rats ; Receptors, Opioid, kappa ; metabolism

Nefopam, a centrally acting analgesic, has been used to control postoperative pain. Reported adverse effects are anticholinergic, cardiovascular or neuropsychiatric. Neurologic adverse reactions to nefopam are confusion, hallucinations, delirium and convulsions. There are several reports about fatal convulsive seizures, presumably related to nefopam. A 71-year-old man was admitted for surgery for a lumbar spinal stenosis. He was administered intravenous analgesics : ketorolac, tramadol, orphenadrine citrate and nefopam HCl. His back pain was so severe that he hardly slept for several days; he even needed morphine and pethidine. At 4 days of administration of intravenous analgesics, the patient suddenly started generalized tonic-clonic seizures for 15 seconds, and subsequently, status epilepticus; these were not responsive to phenytoin and midazolam. After 3 days of barbiturate coma therapy the seizures were controlled. Convulsive seizures related to nefopam appear as focal, generalized, myoclonic types, or status epilepticus, and are not dose-related manifestations. In our case, the possibility of convulsions caused by other drugs or the misuse of drugs was considered. However, we first identified the introduced drugs and excluded the possibility of an accidental misuse of other drugs. Physicians should be aware of the possible occurrence of unpredictable and serious convulsions when using nefopam.
Aged ; Analgesics ; Back Pain ; Coma ; Delirium ; Drug-Related Side Effects and Adverse Reactions ; Hallucinations ; Humans ; Ketorolac ; Meperidine ; Midazolam ; Morphine ; Nefopam* ; Orphenadrine ; Pain, Postoperative ; Phenytoin ; Seizures ; Spinal Stenosis ; Status Epilepticus* ; Tramadol

OBJECTIVETo study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects.

METHODThe CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors.

RESULTCompared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P < 0.01 or P < 0.05), and revealed a remarkably lower dopamine content in VTA, NAc and PFC and the significant increase in the expression of D2 receptor (P < 0.01 or P < 0.05).

CONCLUSIONThe down-regulation of the increased dopamine content in reward nervous circuitry and the up-regulation of the expression of D2 receptor may be one of mechanisms of C. yanhusuo and L-THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

Animals ; Berberine Alkaloids ; administration & dosage ; Brain ; drug effects ; metabolism ; physiopathology ; Conditioning, Operant ; drug effects ; Corydalis ; chemistry ; Dopamine ; metabolism ; Humans ; Male ; Morphine ; adverse effects ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2 ; genetics ; metabolism ; Substance-Related Disorders ; drug therapy ; genetics ; metabolism ; psychology

OBJECTIVE: To observe the protein expression of growth associated protein-43 (GAP-43) in midbrain ventral tegmental area in morphine withdrawal rats at different time, and to evaluate the effect of GAP-43 on morphine withdrawal memory. METHODS: Rat models of morphine dependent 1 week, 2 weeks and 4 weeks were established by morphine hydrochloride intraperitoneal injection with increasing doses to establish natural withdrawal. The protein expression of GAP-43 in midbrain ventral tegmental area was observed by immunohistochemical staining and the results were analyzed by Image-Pro Plus 5.1 image analysis system. RESULTS: With prolongation of dependent time, the expression of GAP-43 was decreased then increased in midbrain ventral tegmental area. CONCLUSION GAP-43 could play a role in morphine withdrawal memory in midbrain ventral tegmental area.
Animals ; Behavior, Animal/drug effects* ; Disease Models, Animal ; Female ; GAP-43 Protein/metabolism* ; Immunohistochemistry ; Male ; Mesencephalon/metabolism* ; Morphine/adverse effects* ; Morphine Dependence/metabolism* ; Naloxone/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome/metabolism* ; Time Factors ; Ventral Tegmental Area/metabolism*

The intrathecal drug delivery system (ITDDS), an effective treatment tool for intractable spasticity and pain, is associated with various complications but breakage of the catheter is rare. We report the case of a 50-yr-old man with ITDDS, in whom an intrathecal catheter was severed, resulting in a 28.6-cm-long intrathecal fragment. The catheter completely retracted into the intrathecal space from the anchor site. The catheter was severed during spine flexion, and the total distal fragment was repositioned in the intrathecal space. Although the outcome of ITDDS was associated with the length or diameter of the broken catheter, no neurologic complications occurred in our patient. Thus, we inserted another catheter instead of removing the old one. Thereafter, the patient has been regularly followed up, and no neurologic complications have developed during the 28 months.
Brachial Plexus/injuries ; Catheters ; Drug Delivery Systems ; *Equipment Failure ; Fluoroscopy ; Humans ; Infusion Pumps, Implantable/*adverse effects ; Injections, Spinal/instrumentation ; Male ; Middle Aged ; Morphine/therapeutic use ; Pain/*drug therapy/etiology

OBJECTIVETo evaluate the effects of morphine infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in ventilated neonates.

METHODSA randomized, double-blind clinical trial was conducted between August 2010 and April 2011 at the neonatal intensive care unit of Nanjing Children's Hospital Affiliated to Nanjing Medical University. A total of 46 ventilated preterm infants (≥ 32 weeks) and term infants were divided into 2 groups at random. Twenty-two infants in test group received a loading dose (100 µg/kg) of morphine (> 1 h) followed by a continuous infusion [10 µg/(kg·h)] for (70.05 ± 29.05) h, and 24 infants in control group received 5% glucose with the same infusion rate. (1) The ventilatory parameters [respiratory rate (R), frequence (f), peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), fraction of inspired oxygen (FiO2)], mean blood pressure (MBP) and heart rate (HR) before treatment, at 30 min, 2 h, 6 h, 12 h, 24 h, 48 h after treatment between two groups were compared. (2) Pain was measured by two assessment tools [neonatal pain, agitation and sedation scale (N-PASS) and COMFORT scale] at the same periods. (3) The ventilation duration, the time from withdrawal to extubation, the total oxygen-inhaled time, the side effects and the clinical outcomes [e.g., pulmonary hemorrhage, air leak, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH)] between two groups were compared.

RESULTS(1) There were no significant differences in the different ventilatory parameters before and after treatment between two groups at different periods (P > 0.05). There was no significant difference in the average blood pressure of two groups at different periods, but the heart rate reduced at 24 - 48 h after treatment in test group with significant difference as compared to control group (t = -2.152 and -2.513, P < 0.05). (2) The N-PASS score and COMFORT score in test group were lower than that in control group at different time points 2 h after treatment (P < 0.05), especially 12 h after treatment (P < 0.01). (3) There were no significant differences in the ventilation duration, the time from withdrawal to extubation and the total oxygen time between two groups, and also in side effects, the incidence of IVH, white matter damage and the clinical outcomes.

CONCLUSIONContinuous infusion of morphine could relieve pain in ventilated neonates, reduce the stress response and promote the human-machine coordination, but the medication did not show any effects on neurobehavioral development and short term outcome.

Analgesics, Opioid ; administration & dosage ; pharmacology ; Double-Blind Method ; Female ; Humans ; Hyaline Membrane Disease ; therapy ; Infant, Newborn ; Infant, Premature ; Infusions, Intravenous ; Intensive Care Units, Neonatal ; Lung Diseases ; therapy ; Male ; Morphine ; administration & dosage ; pharmacology ; Pain ; drug therapy ; etiology ; Pain Measurement ; methods ; Respiration, Artificial ; adverse effects ; Treatment Outcome

OBJECTIVETo explore the effects of intrathecal injection of mitogen-activated protein kinases inhibitors U0126 on the behavioral changes of morphine-induced dependent and withdrawal rats and the expression of nitric oxide synthase (NOS) in spinal cord.

METHODSAll the rats were divided into 4 groups: control group, dependent group, withdrawal group, U0126 group (5 microg). Global withdrawal score, Touch evoked agitation scores (TEA score), immunohistochemical and Western blot technique were undertaken to evaluate behavioral changes and expression of FOS, nNOS and iNOS in spinal cord respectively.

RESULTSThe results showed that intrathecal administration of U0126 significantly alleviated withdrawal symptom, withdrawal scores of U0126 group (22.5 +/- 4.09) were significantly lower than than those of withdrawal group (28.6 +/- 4.89) (P < 0.05). TEA scores of withdrawal group were 13.5 +/- 2.55, which were significantly higher than those of U0126 group (10.0 +/- 2.76, P < 0.05). Fos-like positive neurons in dorsal horn of withdrawal group were 380 +/- 71, which were higher than those of U0126 group(287 +/- 54, P < 0.05). Also nNOS and iNOS positive neurons in dorsal horn of U0126 group were 180 +/- 32, 10.8 +/- 2.8 respectively, which were significantly lower than that of withdrawal group (239 +/- 45, 16.8 +/- 5.1, P < 0.05). Compared with withdrawal group, levels of nNOS and iNOS protein in spinal cord of U0126 group were significantly lower.

CONCLUSIONMEK inhibitors could alleviate withdrawal symptom of morphine-induced dependent rats and could suppress expression of NOS in spinal cord, and extracellular signal-regulate kinase (ERK) might involve the expression of NOS in spinal cord.

Animals ; Behavior, Animal ; drug effects ; Butadienes ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Male ; Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; Morphine ; adverse effects ; Morphine Dependence ; metabolism ; Nitric Oxide Synthase ; metabolism ; Nitriles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism ; Substance Withdrawal Syndrome ; metabolism