BACKGROUNDGabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model.

METHODSGabapentin (2%, 100 mg/kg) or saline (0.5 ml/100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0 - 4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKII were quantified by reverse-transcriptional polymerase chain reaction and Western blotting.

RESULTSThe analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKII and phosphorylated CaMKII in CCI rats.

CONCLUSIONThe analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKII in the spinal cord.

Amines ; therapeutic use ; Analgesics ; therapeutic use ; Animals ; Blotting, Western ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; metabolism ; Cyclohexanecarboxylic Acids ; therapeutic use ; Male ; Neuralgia ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; therapeutic use

The article reviewed clinical studies on painful diabetic peripheral neuropathy (PDPN) treated by integrative medicine. PDPN, a common complication of diabetes mellitus, which could severely influence patients' quality of life. The keystone and difficulty of PDPN treatment is to relieve pain. Tricyclic anti-depressants are the firstline agents for neuropathic pain but with obvious adverse reactions. Antiepileptic drugs and capsicin can relieve PDPN with less adverse reactions. In recent years, lots of report of clinical studies on DPN treated by TCM or integrative medicine were issued, but those pertinent to PDPN were seldom. Only the papers with independent statistical analysis on effect of pain relieving were selected to review in this article, and the authors presumed that it is feasible to treat PDPN with integrative medicine.
Amines ; therapeutic use ; Amitriptyline ; therapeutic use ; Analgesics ; therapeutic use ; Animals ; Antidepressive Agents, Tricyclic ; therapeutic use ; Blood Glucose ; metabolism ; Cyclohexanecarboxylic Acids ; therapeutic use ; Diabetic Neuropathies ; complications ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Pain ; drug therapy ; etiology ; Pain Measurement ; Phytotherapy ; Triazines ; therapeutic use ; gamma-Aminobutyric Acid ; therapeutic use

Animals ; Asthma ; drug therapy ; immunology ; pathology ; Cyclohexanecarboxylic Acids ; therapeutic use ; Cytokines ; physiology ; Eosinophils ; physiology ; Genetic Therapy ; Humans ; Inflammation ; pathology ; Matrix Metalloproteinase 2 ; physiology ; Matrix Metalloproteinase 9 ; physiology ; Nitriles ; Quinolines ; therapeutic use ; Signal Transduction

BACKGROUND: Although both pregabalin and gabapentin are known to be useful for treating lumbar radiating pain and reducing the incidence of surgery, the oral corticosteroids sometimes offer a dramatic effect on severe radiating pain despite the lack of scientific evidence. METHODS: A total of 54 patients were enrolled among 703 patients who complained of lumbar radiating pain. Twenty patients who received an oral corticosteroid was classified as group A and 20 patients who received the control drugs (pregabalin or gabapentin) as group B. Oswestry Disability Index (ODI), Revised Roland Morris disability questionnaire (RMDQ), Short Form 36 (SF-36) questionnaire, lumbar radiating pain, objective patient satisfaction, and objective improvement of patients or physicians were assessed at 2, 6, and 12 weeks after medication. RESULTS: No difference in the sex ratio and age was observed between the groups (p = 0.70 and p = 0.13, respectively). Group A showed greater improvement in radiating pain after 2, 6, and 12 weeks than group B (p < 0.001, p = 0.001, and p < 0.001, respectively). No differences were observed between the groups in satisfaction at the beginning and 12 weeks after taking the medication (p = 0.062 and p = 0.061, respectively) and in objective improvement of patients and physicians (p = 0.657 and p = 0.748, respectively). Group A was less disabled and had greater physical health scores than group B (p = 0.014 and p = 0.017, respectively). CONCLUSIONS: Oral corticosteroids for the treatment of lumbar radiating pain can be more effective in pain relief than gabapentin or pregabalin. The satisfaction of patients and physicians with the drug and objective improvement status were not inferior to that with gabapentin or pregabalin.
Adolescent ; Adrenal Cortex Hormones/*therapeutic use ; Adult ; Aged ; Amines/therapeutic use ; Analgesics/therapeutic use ; Cyclohexanecarboxylic Acids/therapeutic use ; Female ; Humans ; Low Back Pain/*drug therapy/*physiopathology ; Lumbosacral Region/physiopathology ; Male ; Middle Aged ; Patient Satisfaction/statistics & numerical data ; Pregabalin/therapeutic use ; Quality of Life ; Radiculopathy/drug therapy ; Surveys and Questionnaires ; Young Adult ; gamma-Aminobutyric Acid/therapeutic use

We examined the possible anti-inflammatory mechanisms of gabapentin in the attenuation of neuropathic pain and the interaction between the anti-allodynic effects of gabapentin and interleukin-10 (IL-10) expression in a rat model of neuropathic pain. The anti-allodynic effect of intrathecal gabapentin was examined over a 7-day period. The anti-allodynic effects of IL-10 was measured, and the effects of anti-IL-10 antibody on the gabapentin were assessed. On day 7, the concentrations of pro-inflammatory cytokines and IL-10 were measured. Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-alpha, 316.0 +/- 69.7 pg/mL vs 88.8 +/- 24.4 pg/mL; IL-1beta, 1,212.9 +/- 104.5 vs 577.4 +/- 97.1 pg/mL; IL-6, 254.0 +/- 64.8 pg/mL vs 125.5 +/- 44.1 pg/mL; IL-10, 532.1 +/- 78.7 pg/mL vs 918.9 +/- 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody. Expression of pro-inflammatory cytokines was significantly attenuated by daily injections of IL-10. The anti-allodynic effects of gabapentin may be caused by upregulation of IL-10 expression in the spinal cord, which leads to inhibition of the expression of pro-inflammatory cytokines in the spinal cords.
Amines/pharmacology/*therapeutic use ; Analgesics/pharmacology/*therapeutic use ; Animals ; Antibodies/immunology/pharmacology ; Behavior, Animal/drug effects ; Cyclohexanecarboxylic Acids/pharmacology/*therapeutic use ; Cytokines/*metabolism ; Disease Models, Animal ; Injections, Spinal ; Interleukin-10/genetics/immunology/*metabolism ; Male ; Neuralgia/*drug therapy/metabolism/pathology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/biosynthesis/genetics/pharmacology ; Spinal Cord/metabolism ; Up-Regulation ; gamma-Aminobutyric Acid/pharmacology/*therapeutic use

This study was designed to determine whether early gabapentin treatment has a protective analgesic effect on neuropathic pain and compared its effect to the late treatment in a rat neuropathic model, and as the potential mechanism of protective action, the alpha2delta1-subunit of the voltage-dependent calcium channel (alpha2delta1-subunit) was evaluated in both sides of the L5 dorsal root ganglia (DRG). Neuropathic pain was induced in male Sprague-Dawley rats by a surgical ligation of left L5 nerve. For the early treatment group, rats were injected with gabapentin (100 mg/kg) intraperitoneally 15 min prior to surgery and then every 24 hr during postoperative day (POD) 1-4. For the late treatment group, the same dose of gabapentin was injected every 24 hr during POD 8-12. For the control group, L5 nerve was ligated but no gabapentin was administered. In the early treatment group, the development of allodynia was delayed up to POD 10, whereas allodynia was developed on POD 2 in the control and the late treatment group (p<0.05). The alpha2delta1-subunit was up-regulated in all groups, however, there was no difference in the level of the alpha2delta1-subunit among the three groups. These results suggest that early treatment with gabapentin offers some protection against neuropathic pain but it is unlikely that this action is mediated through modulation of the alpha2delta1-subunit in DRG.
Amines/administration & dosage/*therapeutic use ; Analgesics/administration & dosage/*therapeutic use ; Animals ; Calcium Channels/genetics/*metabolism ; Cyclohexanecarboxylic Acids/administration & dosage/*therapeutic use ; Disease Models, Animal ; Injections, Intraperitoneal ; Ligation ; Male ; Neuralgia/*drug therapy/metabolism ; Pain Measurement ; Protein Subunits/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves/surgery ; Up-Regulation ; gamma-Aminobutyric Acid/administration & dosage/*therapeutic use

INTRODUCTIONGabapentin has demonstrated efficacy in clinical trials as a pre-emptive analgesic and in acute postoperative pain management. However, our experience with the drug is still limited. The present study was conducted in order to evaluate the effect of gabapentin on reduction of postoperative pain in the first 24 hours after internal fixation of the tibia under spinal anaesthesia.

METHODSIn a double-blind, randomised controlled clinical trial, 64 American Society of Anesthesiologists Class I or II patients, who underwent internal fixation of the tibia, were administered 300 mg of gabapentin or a placebo two hours before surgery. The postoperative pain was assessed using Visual Analogue Scale two, 12 and 24 hours after surgery. The time from the end of surgery until the first bolus dose of morphine on demand (pain score > 4) and the total morphine requirement were recorded. Patients were also asked about the possible side effects of gabapentin.

RESULTSThe pain score was significantly lower in the gabapentin group at two hours post surgery (p-value is 0.004), while the scores at 12 and 24 hours post surgery were not significantly different between the two groups. No side effect of gabapentin was observed.

CONCLUSIONPre-emptive use of gabapentin 300 mg orally significantly decreases postoperative pain two hours after surgery.

Adult ; Amines ; pharmacology ; therapeutic use ; Anesthesia, Spinal ; methods ; Anesthesiology ; methods ; Cyclohexanecarboxylic Acids ; pharmacology ; therapeutic use ; Double-Blind Method ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Morphine ; therapeutic use ; Orthopedics ; methods ; Pain ; drug therapy ; Pain, Postoperative ; Placebos ; Tibia ; surgery ; Time Factors ; Treatment Outcome ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

OBJECTIVETo study the clinical effects of gabapentin on the treatment of pruritus of scar resulting from deep partial-thickness burn.

METHODSA total of fifty-eight patients suffering from pruritus of scar after deep partial-thickness burn were hospitalized from January 2013 to January 2014. Patients were divided into placebo group (n =18, treated with oral vitamin C in the dose of 100 mg for 4 weeks, twice per day) , cetirizine group (n = 20, treated with oral cetirizine in the dose of 10 mg for 4 weeks, twice per day) , and gabapentin group (n = 20, treated with oral gabapentin in the dose of 300 mg for 4 weeks, twice per day) . Before treatment and on post treatment day (PTD) 3 and 28, the Visual Analog Scale (VAS) was used to assess the itching degree, and the mean scores were recorded. The remission rates of pruritus on PTD 3 and 28 were calculated. The adverse effects were observed during treatment. Data were processed with analysis of variance, q test, and chi-square test.

RESULTSCompared with that before treatment, the itching degree of patients with light, moderate, and severe itching in placebo group was not relieved after treatment; the itching degree of patients with moderate or severe itching in cetirizine group was alleviated after treatment, but not in patients with light itching; itching degree of all patients in gabapentin group was significantly relieved after treatment. There were no obvious differences in VAS scores among the 3 groups before treatment (F = 2.78, P > 0.05). On PTD 3 and 28, the VAS scores of patients in both gabapentin group [(2.3 ± 0.8) and (0.6 ± 0.3) points] and cetirizine group [(4.2 ± 1.7) and (2.8 ± 1.2) points] were lower than those in placebo group [(5.7 ± 2.0) and (5.7 ± 1.9) points, with q values from 6.70 to 7.75, P values below 0.05]. The VAS scores of patients in gabapentin group on PTD 3 and 28 were lower than those in cetirizine group (with q values respectively 6.30 and 6.90, P values below 0.05). The remission rates of pruritus of patients in gabapentin group on PTD 3 and 28 were respectively (66 ± 20)% and (91 ± 17)%, and they were higher than those in cetirizine group [(33 ± 8)% and (56 ± 14)%, with q values respectively 4.70 and 3.82, P values below 0.05]. The remission rate of pruritus of patients in placebo group on PTD 3 and 28 was 0, which was lower than that of the other 2 groups each (with q values from 3.94 to 6.76, P values below 0.05). During the course of treatment, 5 patients in gabapentin group suffered from adverse effects including mild-to-moderate drowsiness and dizziness, but they disappeared one week later. No adverse effects were observed in patients of the other two groups.

CONCLUSIONSFor patients with deep partial-thickness burn, gabapentin can effectively alleviate scar itching after wound healing with safety.

Amines ; administration & dosage ; therapeutic use ; Analgesics ; therapeutic use ; Ascorbic Acid ; administration & dosage ; Burns ; complications ; Cetirizine ; administration & dosage ; Cicatrix ; Cyclohexanecarboxylic Acids ; administration & dosage ; therapeutic use ; Humans ; Pruritus ; drug therapy ; Skin Transplantation ; Treatment Outcome ; Visual Analog Scale ; Wound Healing ; gamma-Aminobutyric Acid ; administration & dosage ; therapeutic use

Spinal gabapentin and adenosine have been known to display an antinociceptive effect. We evaluated the nature of the interaction between gabapentin and adenosine in formalin-induced nociception at the spinal level. Male Sprague-Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 microliter) into the hindpaw. After examination of the effects of gabapentin and adenosine, the resulting interaction was investigated with isobolographic and fractional analyses. Neither gabapentin nor adenosine affected motor function. Gabapentin or adenosine decreased the sum of the number of flinches during phase 2, but not during phase 1 in the formalin test. Isobolographic analysis, in phase 2, revealed an additive interaction between gabapentin and adenosine. Taken together, intrathecal gabapentin and adenosine attenuated the facilitated state and interacted additively with each other.
*Adenosine/administration & dosage/metabolism/therapeutic use ; *Amines/administration & dosage/metabolism/therapeutic use ; *Analgesics/administration & dosage/metabolism/therapeutic use ; Animals ; *Cyclohexanecarboxylic Acids/administration & Dose-Response Relationship, Drug ; Formaldehyde/*toxicity ; Injections, Spinal ; Male ; Motor Activity/physiology ; Pain Measurement ; Rats ; Rats, Sprague-Dawley ; Research Support, Non-U.S. Gov't ; *gamma-Aminobutyric Acid/administration & dosage/metabolism/therapeutic

BACKGROUNDThere is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin.

METHODSForty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed.

RESULTSThe cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P < 0.05, respectively). The injection of 25 mg/kg SB207499 significantly inhibited the increased cough response and airway hyperresponsiveness, the cough frequency and PC150 in guinea pigs were (13 +/- 2) times/3 minutes and (680 +/- 81) microg/ml (P < 0.05), which differed significantly from (18 +/- 2) times/3 minutes and (400 +/- 86) microg/ml after the administration of the same dose of aminophylline (P < 0.05). The inhibition of SB207499 on cough response was dose-dependent. Similarly, SB207499 decreased the total cell number and percentage of eosinophils in bronchoalveolar lavage fluid to (2.1 +/- 0.5) x 10(6)/ml and (20 +/- 5)% respectively, which were significantly different from (3.2 +/- 0.5) x 10(6)/ml and (29 +/- 5)% in the aminophylline group (P < 0.05, respectively) or (4.2 +/- 0.7) x 10(6)/ml and (35 +/- 4)% in the challenge group (P < 0.05, respectively).

CONCLUSIONPhosphodiesterase 4 inhibitor may be more useful than aminophylline for cough associated with eosinophilic airway inflammation via inhibiting airway inflammation and airway hyperresponsiveness.

3',5'-Cyclic-AMP Phosphodiesterases ; antagonists & inhibitors ; Animals ; Bronchial Hyperreactivity ; drug therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Cough ; drug therapy ; Cyclic AMP ; biosynthesis ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Cyclohexanecarboxylic Acids ; therapeutic use ; Dose-Response Relationship, Drug ; Guinea Pigs ; Male ; Nitriles ; Ovalbumin ; immunology ; Phosphodiesterase Inhibitors ; therapeutic use