All about pain pharmacology: what pain physicians should know

From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.

A comparison of 0.075% and 0.15% of ropivacaine with fentanyl for postoperative patient controlled epidural analgesia after laparoscopic gynecologic surgery / 영남의대학술지

BACKGROUND: A motor blockade of lower limbs interferes with early ambulation and limits the usefulness of patient-controlled epidural analgesia (PCEA). The concentration of local anesthetic solution is a major determinant for motor block with PCEA. We compared the effects of epidural infusion of 0.075% ropivacaine with 0.15% epidural ropivacaine on postoperative analgesia, motor block of lower limbs, and other side effects. METHODS: A total of 70 patients undergoing laparoscopic gynecologic surgery received epidural infusions (group R1, 0.15% ropivacaine with fentanyl; group R2, 0.075% ropivacaine with fentanyl). Pain score, motor block, and side effects (hypotension, nausea, vomiting, pruritus, urinary retention, dizziness, and numbness) were measured. RESULTS: There were no significant differences in the demographic profiles between the groups. Pain scores of the group R1 and the group R2 were not significantly different. Motor block was more frequent in the group R1 (0.15% ropivacaine with fentanyl) than in the group R2 (0.075% ropivacaine with fentanyl). CONCLUSION: Lower concentration of ropivacaine (0.075%), when compared with higher concentration of ropivacaine (0.15%), seemed to provide similar analgesia with less motor blockade of the lower limbs for the purpose of PCEA.

A comparison of 0.075% and 0.15% of ropivacaine with fentanyl for postoperative patient controlled epidural analgesia after laparoscopic gynecologic surgery / 영남의대학술지

BACKGROUND: A motor blockade of lower limbs interferes with early ambulation and limits the usefulness of patient-controlled epidural analgesia (PCEA). The concentration of local anesthetic solution is a major determinant for motor block with PCEA. We compared the effects of epidural infusion of 0.075% ropivacaine with 0.15% epidural ropivacaine on postoperative analgesia, motor block of lower limbs, and other side effects.METHODS: A total of 70 patients undergoing laparoscopic gynecologic surgery received epidural infusions (group R1, 0.15% ropivacaine with fentanyl; group R2, 0.075% ropivacaine with fentanyl). Pain score, motor block, and side effects (hypotension, nausea, vomiting, pruritus, urinary retention, dizziness, and numbness) were measured.RESULTS: There were no significant differences in the demographic profiles between the groups. Pain scores of the group R1 and the group R2 were not significantly different. Motor block was more frequent in the group R1 (0.15% ropivacaine with fentanyl) than in the group R2 (0.075% ropivacaine with fentanyl).CONCLUSION: Lower concentration of ropivacaine (0.075%), when compared with higher concentration of ropivacaine (0.15%), seemed to provide similar analgesia with less motor blockade of the lower limbs for the purpose of PCEA.

Ratio of Mediastinal Lymph Node SUV to Primary Tumor SUV in ¹⁸F-FDG PET/CT for Nodal Staging in Non-Small-Cell Lung Cancer / 대한핵의학회잡지

PURPOSE: Following determination of the maximum standardized uptake values (SUVmax) of the mediastinal lymph nodes (SUV-LN) and of the primary tumor (SUV-T) on ¹⁸F-FDG PET/CT in patients with non-small-cell lung cancer (NSCLC), the aim of the study was to determine the value of the SUV-LN/SUV-T ratio in lymph node staging in comparison with that of SUV-LN.METHODS: We retrospectively reviewed a total of 289 mediastinal lymph node stations from 98 patients with NSCLC who were examined preoperatively for staging and subsequently underwent pathologic studies of the mediastinal lymph nodes. We determined SUV-LN and SUV-R for each lymph node station on ¹⁸F-FDG PET/CT and then classified each station into one of three groups based on SUV-T (low, medium and high SUV-T groups). Diagnostic performance was assessed based on receiver operating characteristic (ROC) curve analysis, and the optimal cut-off values that would best discriminate metastatic from benign lymph nodes were determined for each method.RESULTS: The average of SUV-R of malignant lymph nodes was significantly higher than that of benign lymph nodes (0.79±0.45 vs. 0.36±0.23, P<0.0001). In the ROC curve analysis, the area under the curve (AUC) of SUV-R was significantly higher than that of SUV-LN in the low SUV-T group (0.885 vs. 0.810, P= 0.019). There were no significant differences between the AUCs of SUV-LN and of SUV-R in the medium and high SUV-T groups. The optimal cut-off value for SUV-R in the low SUV-T group was 0.71 (sensitivity 87.5 %, specificity 85.9 %).CONCLUSIONS: The SUV-R performed well in distinguishing between metastatic and benign lymph nodes. In particular, SUV-R was found to have a better diagnostic performance than SUV-LN in the low SUV-T group.

High Serum Levels of Thyroid-Stimulating Hormone and Sustained Weight Gain in Patients with Thyroid Cancer Undergoing Radioiodine Therapy

BACKGROUND AND OBJECTIVES: The extent of weight gain and its association with clinical factors in patients undergoing radioiodine therapy for differentiated thyroid cancer remain unclear. We analyzed clinical factors related to sustained weight gain after serum thyroid-stimulating hormone (TSH) stimulation for radioiodine (I-131) therapy. MATERIALS AND METHODS: The study population included 301 adult patients who underwent total thyroidectomy followed by radioiodine therapy and visited the thyroid clinic regularly. Group 1 received a single radioiodine therapy treatment, while group 2 received multiple radioiodine treatment. Data on transient weight gain, defined as weight gain that resolved (±5%) within 1 year after radioiodine therapy, were collected from medical records. Sustained weight gain was defined as body mass index after treatment (BMI(post)) - BMI before treatment (BMI(pre)) ≥2 kg/m2 more than 1 year following radioiodine therapy. Subjective symptoms were scored by questionnaire. Logistic regression analysis was performed using various clinical and laboratory factors to identify risk factors associated with sustained weight gain. RESULTS: Two hundred and fifty-nine (86%) patients showed transient weight gain and 23 (8%) patients showed sustained weight gain. TSH at therapy and T4-on TSH differed significantly in all patients and in the patients in group 1 with sustained weight gain. The proportion of patients with basal BMI≥25 kg/m2 in group 1 with sustained weight gain also differed significantly. Univariate analysis revealed that high serum levels of TSH at therapy (≥100 µIU/mL) and hypercholesterolemia were associated with sustained weight gain in group 1. Multivariate analysis showed that TSH at therapy levels ≥100 µIU/mL was associated with sustained weight gain in group 1. Of 283 patients remaining after excluding those with insufficient TSH suppression during follow-up, T4-on TSH levels were lower in the sustained weight gain group compared to those without sustained weight gain. TSH at therapy levels ≥100 µIU/mL were significantly associated with sustained weight gain in multivariate analysis. CONCLUSION: Most patients (86%) had transient weight gain after TSH at therapy, while 8% of patients showed sustained weight gain. Univariate and multivariate analysis revealed relatively high TSH levels (≥100 µIU/mL) to be a risk factor for patients that received a single dose of radioiodine therapy. Insufficient T4 dose was not associated with sustained weight gain.

Hemodynamic Significance of Internal Carotid or Middle Cerebral Artery Stenosis Detected on Magnetic Resonance Angiography

PURPOSE: We evaluated hemodynamic significance of stenosis on magnetic resonance angiography (MRA) using acetazolamide perfusion single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Of 171 patients, stenosis in internal carotid artery (ICA) and middle cerebral artery (MCA) (ICA-MCA) on MRA and cerebrovascular reserve (CVR) of MCA territory on SPECT was measured using quantification and a 3-grade system. Stenosis and CVR grades were compared with each other, and their prognostic value for subsequent stroke was evaluated. RESULTS: Of 342 ICA-MCA, 151 (44%) presented stenosis on MRA; grade 1 in 69 (20%) and grade 2 in 82 (24%) cases. Decreased CVR was observed in 9% of grade 0 stenosis, 25% of grade 1, and 35% of grade 2. The average CVR of grade 0 was significantly different from grade 1 (p<0.001) and grade 2 stenosis (p=0.007). In quantitative analysis, average CVR index was -0.56+/-7.91 in grade 0, -1.81+/-6.66 in grade 1 and -1.18+/-5.88 in grade 2 stenosis. Agreement between stenosis and CVR grades was fair in patients with lateralizing and non-lateralizing symptoms (kappa=0.230 and 0.346). Of the factors tested, both MRA and CVR were not significant prognostic factors (p=0.104 and 0.988, respectively), whereas hypertension and renal disease were significant factors (p<0.05, respectively). CONCLUSION: A considerable proportion of ICA-MCA stenosis detected on MRA does not cause CVR impairment despite a fair correlation between them. Thus, hemodynamic state needs to be assessed for evaluating significance of stenosis, particularly in asymptomatic patients.

Effective Microorgainsm (EM) Fermentation Extract Attenuates Airway Hyperreactivity and Lung Inflammation In A Mouse Model of Asthma

Effective microorganism (EM) fermentation extract has been widely used for agricultural and environmental application. It has been recently revealed that EM cocktail treatment may be effective for treatment of diseases including cancer. In the present study, effectiveness of EM cocktail to control asthma was investigated using a mouse model of allergic asthma. Asthmatic mice sensitized and intranasally challenged with OVA were orally given EM fermentate (EM-1(R) during antigen challenge. Administration of EM-1(R) resulted in a significant reduction in airway hyper-reactivity (AHR) and airway recruitment of total leukocytes and eosinophils. Cytokine (IL-4, IL-5 and IFNgamma) levels in bronchoalveolar lavage fluid (BALF) and lung tissues were not altered by EM-1(R) treatment. However, IL-13 level in BALF was considerably lower in EM-1(R) treated mice than in controls. Moreover, Ag-specific IL-4, IL-5 and IL-13 production of draining lymph node cells were markedly downregulated by EM-1(R) treatment when compared to controls, whereas their IFNgamma production was not significantly different. Those data show that EM-1(R) treatment suppresses type 2 helper T (Th2), but not type 1 helper T (Th1), cell response. This finding was also supported by serum antibody data showing that IgE and IgG1 levels in EM-1(R) treated mice were significantly lower than in controls, while IgG2a level was not significantly different between two groups. In conclusion, oral administration of EM-1(R) attenuates asthmatic manifestations including AHR and airway recruitment of eosinophils in a mouse model and which possibly results from selective inhibition of Th2 cell response to allergen. Our data also suggest that EM-1(R) may be effectively applied for control of allergic asthma.

Effective Microorgainsm (EM) Fermentation Extract Attenuates Airway Hyperreactivity and Lung Inflammation In A Mouse Model of Asthma

Effective microorganism (EM) fermentation extract has been widely used for agricultural and environmental application. It has been recently revealed that EM cocktail treatment may be effective for treatment of diseases including cancer. In the present study, effectiveness of EM cocktail to control asthma was investigated using a mouse model of allergic asthma. Asthmatic mice sensitized and intranasally challenged with OVA were orally given EM fermentate (EM-1(R) during antigen challenge. Administration of EM-1(R) resulted in a significant reduction in airway hyper-reactivity (AHR) and airway recruitment of total leukocytes and eosinophils. Cytokine (IL-4, IL-5 and IFNgamma) levels in bronchoalveolar lavage fluid (BALF) and lung tissues were not altered by EM-1(R) treatment. However, IL-13 level in BALF was considerably lower in EM-1(R) treated mice than in controls. Moreover, Ag-specific IL-4, IL-5 and IL-13 production of draining lymph node cells were markedly downregulated by EM-1(R) treatment when compared to controls, whereas their IFNgamma production was not significantly different. Those data show that EM-1(R) treatment suppresses type 2 helper T (Th2), but not type 1 helper T (Th1), cell response. This finding was also supported by serum antibody data showing that IgE and IgG1 levels in EM-1(R) treated mice were significantly lower than in controls, while IgG2a level was not significantly different between two groups. In conclusion, oral administration of EM-1(R) attenuates asthmatic manifestations including AHR and airway recruitment of eosinophils in a mouse model and which possibly results from selective inhibition of Th2 cell response to allergen. Our data also suggest that EM-1(R) may be effectively applied for control of allergic asthma.