minocycline and Pain--Postoperative

There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery.. This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter-Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of postoperative cognitive dysfunction was judged from the results of the neurocognitive test battery, with consideration of the learning effect. The secondary endpoints were the effects of minocycline on postoperative delirium and postoperative pain.. A total of 100 patients were randomized to the minocycline group, and 102 were randomized to the placebo group. The average age of patients was 75 yr. Evaluation showed no significant difference in the incidence of postoperative cognitive dysfunction between the minocycline and placebo groups at both 1 week (8 of 90 [8.9%] vs. 4 of 95 [4.2%]; odds ratio, 2.22 [95% CI, 0.64 to 7.65]; P = 0.240) and 3 months (15.3 of 90 [17.0%] vs. 15.3 of 95 [16.1%]; odds ratio, 1.07 [95% CI, 0.49 to 2.32]; P = 0.889) postoperatively. Missing data 3 months after surgery were corrected by the multiple imputation method. There were no differences between the two groups in postoperative delirium and postoperative pain.. Minocycline is likely to have no preventive effect on postoperative cognitive dysfunction.

Topics: Aged; Arthroplasty, Replacement, Knee; Cognitive Dysfunction; Double-Blind Method; Emergence Delirium; Humans; Minocycline; Pain, Postoperative; Postoperative Cognitive Complications

Minocycline strongly inhibits microglial activation, which contributes to central sensitization, a major mechanism underlying chronic pain development. We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy. We randomly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups. The minocycline group received 100mg minocycline orally, twice daily, beginning the evening before surgery and continuing for 8 days. The primary outcome was the change in lower limb pain intensity at rest between baseline and 3 months. Secondary outcomes were pain intensity on movement, the incidence of persistent pain and chronic neuropathic pain, back pain intensity at rest and on movement, and changes in Neuropathic Pain Symptom Inventory, Brief Pain Inventory, and Roland-Morris scores at 3 months. An intention-to-treat analysis was performed for patients assessed from the day before surgery to 3 months. The decrease in lower limb pain intensity was similar in the placebo and minocycline groups, both at rest -1.7 ± 1.6 vs -2.3 ± 2.4 and on movement -2.5 ± 2.1 vs -3.4 ± 2.9. The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups. Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline. Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy.

Topics: Adult; Analgesia; Diskectomy; Double-Blind Method; Female; Follow-Up Studies; Humans; Lumbar Vertebrae; Male; Middle Aged; Minocycline; Pain Measurement; Pain, Postoperative; Treatment Outcome

The purpose of this study is to evaluate and compare the clinical and radiographic effectiveness of Ciprofloxacin, Minocycline, Metronidazole combination with Ciprofloxacin, Minocycline and Tinidazole combination when used for Lesion Sterilization and Tissue Repair in primary teeth.. 25 healthy children, visiting Dept. of Pediatric & Preventive Dentistry, D.A.P.M.R.V. Dental College, Bangalore, India, aged between 6-9 years who were having 30 infected primary teeth are selected and divided into 2 groups. In Group A, a mixture of 3mix-MP Ciprofloxacin, Metronidazole and Minocycline was placed on the floor of the pulp chamber covering the root canal orifices. In Group B a mixture of Ciprofloxacin, Tinidazole and Minocycline was placed as a layer on the floor of the pulp chamber. The procedure was completed in a single visit. Post operative clinical evaluation was done after 1,6,12 and 24 months. Postoperative radiographic evaluation was done at 6, 12 and 24 months.. No statistically significant difference is observed between both the groups and a combination of Ciprofloxacin, Minocycline and Tinidazole antibacterial drugs can be used on teeth pulpally involved with physiologic root resorption.. After a 24 Month follow up, we can conclude that primary teeth with the periradicular lesions, can be conserved by using combination of Ciprofloxacin, Minocycline and Tinidazole antibacterial drugs.

Topics: Anti-Bacterial Agents; Child; Ciprofloxacin; Dental Pulp Necrosis; Double-Blind Method; Drug Combinations; Humans; Metronidazole; Minocycline; Pain, Postoperative; Periapical Abscess; Radiography; Regeneration; Root Canal Irrigants; Root Resorption; Tinidazole; Tooth Mobility; Tooth, Deciduous; Treatment Outcome

To assess the impact of cryotherapy or topical minocycline on patients' perceptions of recovery from pain after third molar surgery in an exploratory comparative-effectiveness study.. Subjects aged at least 14 years who were having all 4 third molars removed were enrolled in 3 separate institutional review board-approved studies. Study groups included subjects treated with a passively applied cold wrap for 24 hours postoperatively, subjects treated with topical minocycline during surgery, and subjects enrolled in a nonconcurrent comparison group who had received neither topical minocycline nor directed cryotherapy. Third molar surgery was performed in all cases by trained surgeons using the same protocol. An exact Kruskal-Wallis test was used to compare the distributions of the worst and average pain scores and a Fisher exact test to compare verbal responses from Gracely pain scales among the 3 groups for postsurgical days (PSDs) 1 to 3.. This study comprised 51 cryotherapy subjects (2005-2009), 63 minocycline subjects (2003-2004), and 92 comparison-group subjects (2002-2006) who were treated at academic centers and in community practices across the United States (N = 206). Demographic descriptors were similar among all groups. For PSDs 1 through 3 (unadjusted), the highest scores for worst pain (6-7 [out of 7] on Likert-type scale) were reported less frequently in each of the study groups than in subjects in the comparison group, although the numbers of subjects reporting the highest scores were few. The distribution of pain outcomes was significantly different among the 3 groups for worst pain and affective words on PSD 1 (P = .04 for both). However, the small number of subjects who reported the highest pain scores precluded adequate multivariate statistical analyses for all outcomes on PSD 1 to 3.. Data from this exploratory study suggest that adjunctive therapy to decrease postoperative pain-cryotherapy or topical minocycline-might be effective at moderating the patient's highest pain levels after third molar surgery. The topic should be studied further in a multicenter, prospective, randomized trial.

Topics: Administration, Topical; Adolescent; Adult; Analgesics; Anti-Bacterial Agents; Combined Modality Therapy; Cryotherapy; Ethnicity; Female; Humans; Male; Mandible; Minocycline; Molar, Third; Osteotomy; Pain Measurement; Pain, Postoperative; Prospective Studies; Tooth Extraction; Young Adult

Compare recovery for clinical and health-related quality of life (HRQOL) outcomes after third molar surgery in patients treated with or without topical minocycline at surgery.. Sixty-three patients at least 18 years of age with all 4 third molars below the occlusal plane were treated with topical minocycline during third molar surgery. Topical minocycline (1.0 mg in bioresorbable polyglycolide-co-dl-lactide [PGLA] sustained-release microspheres) was placed sequentially in bony defects after removal of lower third molars. Clinical and health-related quality of life (HRQOL) outcomes of these patients postsurgery were compared with those of a nonconcurrent control group (n = 60 patients) who did not receive antibiotics. The control group was selected using the same criteria and treated under the same surgical protocol as the antibiotic group. Differences between the groups were assessed with Cochran-Mantel-Haenszel row mean score statistics.. The 63 patients in the minocycline group were treated at 4 clinical centers. The incidence of delayed clinical recovery, defined as a postsurgery visit with treatment, was significantly lower in the minocycline group compared with the control group. In the minocycline group, 10% had 1 postsurgery visit with treatment; no patient had 2 visits. In the control group without antibiotics, 28% had at least 1 postsurgery visit with treatment (P = .01) and 13% had at least 2 postsurgery visits with treatment. Recovery time to "no" or "little trouble" with chewing and mouth opening was significantly improved in the minocycline group (P < .05).. Administration of topical minocycline with third molar surgery may improve clinical and HRQOL recovery in healthy adult patients with all 4 third molars below the occlusal plane, a presenting characteristic that has been suggested as a risk factor for delayed recovery.

Topics: Administration, Topical; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Female; Humans; Male; Minocycline; Molar, Third; Pain, Postoperative; Quality of Life; Recovery of Function; Statistics, Nonparametric; Tooth Extraction; Treatment Outcome; Wound Healing

This study verified that sleep deprivation before and after skin/muscle incision and retraction (SMIR) surgery increased the risk of chronic pain and investigated the underlying roles of microglial voltage-dependent anion channel 1 (VDAC1) signaling.. Adult mice received 6 hours of total sleep deprivation from 1 day prior to SMIR until the third day after surgery. Mechanical and heat-evoked pain was assessed before and within 21 days after surgery. Microglial activation and changes in VDAC1 expression and oligomerization were measured. Minocycline was injected to observe the effects of inhibiting microglial activation on pain maintenance. The VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and oligomerization inhibitor VBIT-4 were used to determine the roles of VDAC1 signaling on microglial adenosine 5' triphosphate (ATP) release, inflammation (IL-1β and CCL2), and chronicity of pain.. Sleep deprivation significantly increased the pain duration after SMIR surgery, activated microglia, and enhanced VDAC1 signaling in the spinal cord. Minocycline inhibited microglial activation and alleviated sleep deprivation-induced pain maintenance. Lipopolysaccharide (LPS)-induced microglial activation was accompanied by increased VDAC1 expression and oligomerization, and more VDAC1 was observed on the cell membrane surface compared with control. DIDS and VBIT-4 rescued LPS-induced microglial ATP release and IL-1β and CCL2 expression. DIDS and VBIT-4 reversed sleep loss-induced microglial activation and pain chronicity in mice, similar to the effects of minocycline. No synergistic effects were found for minocycline plus VBIT-4 or DIDS.. Perioperative sleep deprivation activated spinal microglia and increases the risk of chronic postsurgical pain in mice. VDAC1 signaling regulates microglial activation-related ATP release, inflammation, and chronicity of pain.

Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Adenosine Triphosphate; Animals; Inflammation; Lipopolysaccharides; Mice; Microglia; Minocycline; Pain, Postoperative; Sleep Deprivation; Voltage-Dependent Anion Channel 1

Activated astrocytes play important roles in chronic post-surgical pain (CPSP). Recent studies have shown reactive astrocytes are classified into A1 and A2 phenotypes, but their precise roles in CPSP remain unknown. In this study, we investigated the roles of spinal cord A1 and A2 astrocytes and related mechanisms in CPSP.. We used a skin/muscle incision and retraction (SMIR) model to establish a rat CPSP model. Microglia, CXCR7, and the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways were regulated by intrathecal injections of minocycline (a non-specific microglial inhibitor), AMD3100 (a CXCR7 agonist), and LY294002 (a specific PI3K inhibitor), respectively. Mechanical allodynia was detected with von Frey filaments. The changes in microglia, A1 astrocytes, A2 astrocytes, CXCR7, and PI3K/Akt signaling pathways were examined by enzyme-linked immunosorbent assay (ELISA), western blot, and immunofluorescence.. Microglia were found to be activated, with an increase in interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q) in the spinal cord at an early stage after SMIR. On day 14 after SMIR, spinal cord astrocytes were also activated; these were mainly of the A1 phenotype and less of the A2 phenotype. Intrathecal injection of minocycline relieved SMIR-induced mechanical allodynia and reverted the ratio of A1/A2 reactive astrocytes. The expression of CXCR7 and PI3K/Akt signaling was decreased after SMIR, while they were increased after treatment with minocycline. Furthermore, intrathecal injection of AMD3100 also relieved SMIR-induced mechanical allodynia, reverted the ratio of A1/A2 reactive astrocytes, and activated the PI3K/Akt signaling pathway, similar to the effects produced by minocycline. However, intrathecal injection of AMD3100 did not increase the analgesic effect of minocycline. Last, LY294002 inhibited the analgesic effect and A1/A2 transformation induced by minocycline and AMD3100 after SMIR.. Our results indicated that microglia induce the transformation of astrocytes to the A1 phenotype in the spinal cord via downregulation of the CXCR7/PI3K/Akt signaling pathway during CPSP. Reverting A1 reactive astrocytes to A2 may represent a new strategy for preventing CPSP.

Topics: Animals; Anti-Bacterial Agents; Astrocytes; Male; Microglia; Minocycline; Pain, Postoperative; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Receptors, CXCR

Neonatal surgical injury exacerbates spinal microglial reactivity, modifies spinal synaptic function, leading to exaggerated pain hypersensitivity after adult repeated incision. Whether and how the alteration in microglial reactivity and synaptic plasticity are functionally related remain unclear. Previously, we and others have documented that spinal brain-derived neurotrophic factor (BDNF), secreted from microglia, contributes to long-term potentiation (LTP) in adult rodents with neuropathic pain. Here, we demonstrated that the mRNA and protein expression of spinal BDNF are significantly upregulated in adult rats subjected to neonatal incision and adult repeated incision (nIN-IN). Neonatal incision facilitates spinal LTP induced by BDNF or high frequency electrical stimulation after adult incision, including a decreased induction threshold and an increased magnitude of LTP. Coincidently, inhibition of spinal BDNF abrogates the LTP facilitation, alleviates the mechanical allodynia and thermal hyperalgesia in nIN-IN rats. By contrast, spinal application of exogenous BDNF in the adult rats with a single neonatal incision mimics the LTP facilitation and pain hypersensitivity, which have been found in nIN-IN rats. Exogenous BDNF-induced exacerbation of pain hypersensitivity could be blocked by BDNF inhibitor. In addition, blockade of microglial reactivity by intrathecal application of minocycline attenuates the elevation of BDNF and the LTP facilitation, and also, alleviates pain hypersensitivity in nIN-IN rats. In conclusion, spinal BDNF, at least partly derived from microglia, contributes to the neonatal incision-induced facilitation of spinal LTP and to the exacerbation of incisional pain in adult rats. Thus, spinal BDNF may combine the changes of microglial reactivity and synaptic plasticity in nIN-IN rats.

Topics: Analgesics, Non-Narcotic; Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Female; Hot Temperature; Hyperalgesia; Long-Term Potentiation; Male; Microglia; Minocycline; Pain, Postoperative; Random Allocation; Rats, Sprague-Dawley; RNA, Messenger; Spinal Cord; Touch; Wounds and Injuries

Postoperative pain control contributes to quality of life. Activation of spinal cord microglia after peripheral nerve injury contributes to mechanical hypersensitivity. The contribution of spinal cord microglia to hypersensitivity after surgery, however, is not well understood. Here, the authors evaluated whether inhibition of spinal microglia reduced postoperative mechanical hypersensitivity, and if so, whether the effect differed from that in a rat neuropathic pain model.. Male Sprague-Dawley rats underwent either unilateral plantar hind paw incision (postoperative pain model) or L5 spinal nerve transection (neuropathic pain model), and the development of mechanical hypersensitivity was assessed using von Frey filaments. The microglial inhibitor minocycline was intraperitoneally administered daily for either 3 or 7 days. Spinal microglial activation was evaluated by OX42 immunohistochemistry. We also tested the effect of intrathecal administration of a p38 mitogen-activated protein kinase inhibitor, SB203580.. In the postoperative pain model, minocycline did not suppress mechanical hypersensitivity, but did inhibit an increase in spinal OX42 expression. In contrast, in the neuropathic pain model, minocycline reduced mechanical hypersensitivity in a dose-related manner and inhibited spinal OX42 expression. SB203580 attenuated hypersensitivity in the neuropathic pain model, but not in the postoperative pain model.. The results of the present study suggest that spinal OX42 expression has a more important role in the development of neuropathic pain than in postoperative pain, and that an increase in spinal OX42 expression does not contribute to postoperative mechanical hypersensitivity.

Topics: Animals; Anti-Bacterial Agents; Behavior, Animal; CD11b Antigen; Enzyme Inhibitors; Fluorescent Antibody Technique; Hyperalgesia; Imidazoles; Immunohistochemistry; Male; Microglia; Minocycline; p38 Mitogen-Activated Protein Kinases; Pain; Pain, Postoperative; Peripheral Nervous System Diseases; Pyridines; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Nerves