Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel alpha2-delta ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.
Analgesics, Opioid ; Antidepressive Agents ; Calcium Channels ; Capsaicin ; Chronic Pain ; Fibromyalgia ; Lidocaine ; Ligands ; Mexiletine ; N-Methylaspartate ; Neuralgia ; Neuromuscular Agents ; Norepinephrine ; Pain Management ; Serotonin ; Sleep Deprivation ; Tramadol

Chronic perineal pain is an often encountered problem, which produces a great degree of functional impairment and frustration to the patient and a challenge to the treating physician. The reason for this problem is that the region contains diverse anatomic structures with mixed somatic, visceral and autonomic innervations affecting bladder and bowel control and sexual function. A blockade of nociceptive and sympathetic supply to the perineal region, supplied through the ganglion impar has been shown to benefit patients with chronic perineal pain. Several options to this block have been described that chemical neurolysis, radiofrequency ablation etc. Although the analgesic effect of Botulinum toxin type A (BoNT-A) has long been considered secondary to its action for muscle relaxation, BoNT-A also affects the release of the neurotransmitters that are involved in pain perception. We describe a patient who was successfully given ganglion impar block with BoNT-A.
Botulinum Toxins ; Botulinum Toxins, Type A ; Frustration ; Ganglion Cysts ; Humans ; Muscle Relaxation ; Nerve Block ; Neurotransmitter Agents ; Pain Perception ; Urinary Bladder

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious complications associated with anticancer drugs. CIPN leads to a lower quality of life and dysfunction of the sensory, motor, and autonomic systems, and often causes patients to discontinue chemotherapy. It is usually misdiagnosed and undertreated due to a lack of consensus and unclear pathophysiology, for which many mechanisms have been suggested, including mitochondrial dysfunction, various pain mediators, abnormal spontaneous discharge in A and C fibers, and others. To date, no agents have been shown to effectively prevent CIPN, leading to debate as to the standard protocol. Duloxetine has demonstrated a moderate therapeutic effect against CIPN. Although tricyclic antidepressants (such as nortriptyline or desipramine), gabapentin, and a topical gel containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg) showed inconclusive results in CIPN trials, these agents are currently considered the best options for CIPN treatment. Therefore, further studies on the pathophysiology and treatment of CIPN are needed.
Amitriptyline ; Antidepressive Agents, Tricyclic ; Baclofen ; Consensus ; Drug Therapy* ; Humans ; Ketamine ; Nerve Fibers, Unmyelinated ; Neuralgia* ; Nortriptyline ; Peripheral Nervous System Diseases ; Quality of Life ; Duloxetine Hydrochloride

BACKGROUND: Cardiovascular risk factors have been divided into 2 categories, modifiable risk factors, and nonmodifiable risk factors. Clustering of risk factors may increase the risk of CAD more than any of the factors alone and often related to each other. We conducted this study to examine clustering of modifiable risk factors, to analyse associated factors with the clustering of metabolic risk factors, and to evaluate the risk of CAD according to the number of cardiovascular risk factors. METHODS: The case series comprised of 166 patients with angiographically confirmed coronal artery disease, who were admitted to the Division of Cardiology of a Medical Center in Seoul. The controls were 137 persons composed of patients with normal coronary arteriogram or patients with normal myocardial SPECT for chest pain. We surveyed their life style habits, measured anthropometric variables, and analyzed biochemical markers among CAD patients and controls. RESULTS: Modifiable risk factors, smoking, hypertension, diabetes, hyperchesterolemia, and low HDL-C were clustering each others among middle-aged Korean. Clustering of metabolic risk factors, hypertension diabetes, hyperchesterolemia, and low HDL-C were associated with white-collar griup, low physucal activity, non-exercise, high BMI(body mass index) and high WHR(waist-hip ratio). The odds ratios for CAD in men with 3,4 more than 5 risk factors were 2.0(95% Cl : 0.9-4.5), 2.9(95% Cl : 1.2-6.7), and 12.2(95% Cl 3.5-42.0) respectively, compared with men with less than 2risk factors. The corresponding odds ratios in women were 3.4(95% Cl : 1.3-9.0),71(95% Cl : 1.2-13.5), and 4.5(95% Cl : 1.0-21.5) respectively. CONCLUSION: These findings show that modifiable cardiovascular risk factors cluster among middle-aged Korean. The more the cardivascular risk factors, the higher the CAD risk in men and not only for clustering cardiovascular risk factors but also for CAD risk.
Arteries* ; Biomarkers ; Cardiology ; Chest Pain ; Cluster Analysis* ; Coronary Artery Disease ; Female ; Humans ; Hypertension ; Life Style ; Male ; Odds Ratio ; Risk Factors* ; Seoul ; Smoke ; Smoking ; Tomography, Emission-Computed, Single-Photon

Endotracheal tube obstruction causes serious complications, including cardiovascular instability, pneumothorax, pulmonary edema and brain death. A 64 year old man was scheduled for a laminectomy and instrument fixation due to spinal stenosis. The patient was intubated with a 8.5 mm reinforced endotracheal tube and turned to the prone position. An hour later, signs of partial endotracheal obstruction were observed including high airway pressure and low tidal volume. Airway obstruction signs were aggravated as the operation proceeded. Two hour later, passage of a suction catheter was difficult and PaCO2 increased significantly, so we temporarily stopped the operation and turned the patient to supine. After that, we exchanged the tube with another tube and found the distal tip of the reinforced tube impacted with mucous secretions.
Airway Obstruction ; Brain Death ; Catheters ; Humans ; Intubation ; Laminectomy ; Middle Aged ; Pneumothorax ; Prone Position ; Pulmonary Edema ; Spinal Stenosis ; Suction ; Tidal Volume

BACKGROUND: Neostigmine, a cholinesterase inhibitor, is known to reverse the neuromuscular blocking action induced by nondepolarizing muscle relaxants at the end of general anesthesia. Some authors, however, reported that neostigmine has the properties of a neuromuscular block in skeletal muscles while others reported that neostigmine caused the smooth muscles such as the diaphragm to relax rather than to contract. The purpose of this study was to evaluate the effect of neostigmine at different doses on the tracheal smooth muscle in rabbits. METHODS: Isolated tracheal ring preparation in rabbits was used. Groups were divided into 7 groups; acetylcholine group (acetylcholine cumulative administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), neostigmine group (neostigmine cumulative administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), acetylcholine 10 6 M + neostigmine group (acetylcholine 10 6 M prior to neostigmine administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), acetylcholine 10 4 M + neostigmine group (acetylcholine 10 4 M prior to neostigmine administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), neostigmine 10 5, 10 4 and 10 3 M groups (neostigmine administered at doses of 10 5, 10 4 and 10 3 M). Smooth muscle contraction was evaluated in isometric tension per gram of tissue. RESULTS: In the acetylcholine group, the contractions increased as the dosage increased (10 8 10 3 M). In the neostigmine group, the contractions increased as the dosage increased (10 8 10 4 M), but at 10 3 M of neostigmine, contractions suddenly decreased. In addition when acetylcholine 10 6 M was given as a pretreatment, there was a sudden decrease in muscle contractions induced by neostigmine at 10 3 M. Also the contractions induced by 10 3 M neostigmine were less than that of 10 4 and 10 5 M. CONCLUSIONS: We concluded that neostigmine caused smooth muscle contraction at low concentrations by blocking acetylcholine metabolism, but at high concentrations, smooth muscle contractions were decreased and this might be due to direct action at the acetylcholine receptor.
Acetylcholine ; Anesthesia, General ; Cholinesterases ; Diaphragm ; Metabolism ; Muscle Contraction ; Muscle, Skeletal ; Muscle, Smooth* ; Neostigmine* ; Neuromuscular Blockade ; Rabbits*

Aged ; Bone Marrow ; diagnostic imaging ; pathology ; Epidural Space ; diagnostic imaging ; pathology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnostic imaging ; pathology ; Male ; Sarcoma, Myeloid ; diagnostic imaging ; pathology ; Spinal Cord Compression ; diagnostic imaging ; pathology

BACKGROUND: Soluble epoxide hydrolase (sEH) is an enzyme that converts epoxyeicosatrienoic acid (EET) into the anti-inflammatory dihydroxyeicosatrienoic acids (DHET). Inhibition of sEH by the potent soluble epoxide hydrolase inhibitor (sEHI) decreases inflammation by increasing EET. The K/BxN serum transfer mouse model of arthritis displays an initial inflammation and an associated tactile allodynia that continues on following the resolution of inflammation. METHODS: We undertook the following studies: i) Using the K/BxN mouse model, we examined effects on allodynia during the early inflammatory phase of administration of sEHI 3 mg/kg and/or diclofenac (DFC) 10 mg/kg. ii) In the late inflammatory phase, we administered sEHI (3, 10, or 30 mg/kg); DFC 10 mg/kg; gabapentin 100 mg/kg. iii) Using the conditioned place preference (CPP) we examined the synergism between sEHI and DFC in the K/BxN mouse using the CPP paradigm. The drug was administered intraperitoneally and the allodynia was measured with the von Frey test. RESULTS: In the early phase, both sEHI and DFC displayed an antiallodynic action. In the late phase, sEHI, and gabapentin but not DFC were effective in reversing the allodynia. Comparable results were observed with the CPP. CONCLUSIONS: This study demonstrates that sEHI reduces mechanical allodynia in both the early and the late inflammatory K/BxN mouse model of arthritis. The sEHI target thus addresses the hyperalgesia arising from inflammation as well as the post-inflammatory phase that has been said to reflect neuropathic-like states, thus presenting alternatives to the limited efficacy of arthritis drugs in use.
Animals ; Arthritis* ; Diclofenac ; Hyperalgesia ; Inflammation ; Mice*

BACKGROUND: Cytokines are important mediators of immune response to surgery and pain.The aim of the study was to investigate the effect of remifentanil on serum levels of cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), in patients undergoing laparoscopic hysterectomy. METHODS: Twenty four patients scheduled for laparoscopic hysterectomy were randomly assigned to control or remifentanil group.Both groups received 1.5-2.5% end tidal concentration of sevoflurane and air in 50% oxygen.Remifentanil group received a bolus of remifentanil 1microgram/kg over 1 min and an infusion of remifentanil at a rate of 0.1microgram/kg/min.Control group received 10 ml saline (placebo) and an infusion of saline at the same rate. Venous blood samples for measurement of serum cytokine concentrations were taken before anesthesia (T1), at 2 h after infusion (T2), and at the 1 hour after surgery (T3). RESULTS: Serum TNF-alpha concentration did not differ significantly over time in both groups.Serum TNF-alpha concentration was higher in remifentanil group at T3 (9.76 +/- 1.19 pg/ml vs.8.53 +/- 0.71 pg/ml) than in control group (P < 0.05). In both groups, serum IL-6 concentrations were significantly higher at T3, when compared to those at T1 and T2 (P < 0.05). CONCLUSIONS: Remifentanil did not attenuate early postoperative change of serum TNF-alpha and IL-6 concentrations in patients undergoing laparoscopic hysterectomy. Serum IL-6 level increased at postoperative 1 h, regardless of remifentanil use.
Anesthesia ; Cytokines ; Humans ; Hysterectomy ; Interleukin-6 ; Methyl Ethers ; Piperidines ; Tumor Necrosis Factor-alpha

Benzoylureas are chemical compounds best known for their use as insecticides. Diflubenzuron is one of the more commonly used benzoylurea pesticides. Others include chlorfluazuron, flufenoxuron, hexaflumuron, and triflumuron. They act as insect growth regulators by inhibiting synthesis of chitin in the body of the insect. They have low toxicity in mammals because mammals have no chitin. Chlorfluazuron insecticides, which are mixed with solvent naphatha, are commonly used. Thus we assume that in the presented case mental change outcome of poisoning was connected with toxic effects of solvent naphtha rather than with chlorfluazuron action. Components of solvent naphtha, particularly trimethylbenzenes, exert strong irritant action on the gastric mucosa and are very well absorbed from the gastrointestinal tract. We report on a 67-year-old man with stuporous mentality after intentional ingestion of approximately 200 ml of liquid chlorfluazuron in a suicide attempt. He was discharged after conservative treatments including gastric irrigation, charcoal, mechanical ventilation, hydration, and antibiotics for aspiration pneumonia without complications.
Aged ; Anti-Bacterial Agents ; Charcoal ; Chitin ; Diflubenzuron ; Eating ; Gastric Lavage ; Gastric Mucosa ; Gastrointestinal Tract ; Humans ; Insecticides ; Insects ; Juvenile Hormones ; Mammals ; Pesticides ; Pneumonia, Aspiration ; Poisoning* ; Respiration, Artificial ; Stupor ; Suicide