Longitudinal peripheral tissue RNA-Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model.

Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic behavioral tests, histological analyses, and next-generation RNA sequencing, respectively. The most rapidly (1 hour) expressed genes were the chemokines, Cxcl1 and Cxcl2. Consequently, infiltrating leukocytes were abundantly observed starting at 6 and peaking at 24 hours after incising which was supported by histological analysis and appearance of the neutrophil markers, S100a8 and S100a9. At this time, hyperalgesia was at a peak and overall transcriptional activity was most highly activated. At the 1-day timepoint, Nppb, coding for natriuretic peptide precursor B, was the most strongly upregulated gene and was localized by in situ hybridization to the epidermal keratinocytes at the margins of the incision. Nppb was basically unaffected in a peripheral inflammation model transcriptomic dataset. At the late phase of wound healing, five secreted, incision-specific peptidases, Mmp2, Aebp1, Mmp23, Adamts7, and Adamtsl1, showed increased expression, supporting the idea of a sustained tissue remodeling process. Transcripts that are specifically upregulated at each timepoint in the incision model may be potential candidates for either biomarkers or therapeutic targets for wound pain and wound healing. This study incorporates the examination of longitudinal temporal molecular responses, corresponding anatomical localization, and hyperalgesic behavioral alterations in the surgical incision model that together provide important and novel foundational knowledge to understand mechanisms of wound pain and wound healing.

Utilization and evolving prescribing practice of opioid and non-opioid analgesics in patients undergoing lymphadenectomy for cutaneous malignancy.

BACKGROUND AND OBJECTIVES: Opioids are commonly prescribed following surgery and can lead to persistent opioid use. We assessed changes in prescribing practices following an opioid education initiative for patients undergoing lymphadenectomy for cutaneous malignancy. METHODS: A single-institution retrospective study of all eligible patients (3/2016-3/2020) was performed. RESULTS: Indications for lymphadenectomy in 328 patients were metastatic melanoma (84%), squamous cell carcinoma (10%), and Merkel cell carcinoma (5%). At discharge, non-opioid analgesics were increasingly utilized over the 4-year study period, with dramatic increases after education initiatives (32%, 42%, 59%, and 79% of pts, respectively each year; p < 0.001). Median oral morphine equivalents (OMEs) prescribed also decreased dramatically starting in year 3 (250, 238, 150, and 100 mg, respectively; p < 0.001). Patients discharged with 200 mg OMEs were less likely to also be discharged with non-opioid analgesics (40% vs. 64%. respectively, p < 0.001). CONCLUSIONS: Analgesic prescribing practices following lymphadenectomy for cutaneous malignancy improved significantly over a 4-year period, with use of non-opioids more than doubling and a 60% reduction in median OME. Opportunities exist to further increase non-opioid use and decrease opioid dissemination after lymphadenectomy for cutaneous malignancy.

Opioid prescribing exceeds consumption following common surgical oncology procedures.

BACKGROUND AND OBJECTIVES: Surgical oncology patients are vulnerable to persistent opioid use. As such, we aim to compare opioid prescribing to opioid consumption for common surgical oncology procedures. METHODS: We prospectively identified patients undergoing common surgical oncology procedures at a single academic institution (August 2017-March 2018). Patients were contacted by telephone within 6 months of surgery and asked to report their opioid consumption and describe their discharge instructions and opioid handling practices. RESULTS: Of the 439 patients who were approached via telephone, 270 completed at least one survey portion. The median quantity of opioid prescribed was significantly larger than consumed following breast biopsy (5 vs. 2 tablets of 5 mg oxycodone, p < .001), lumpectomy (10 vs. 2 tablets of 5 mg oxycodone, p < .001), and mastectomy or wide local excision (20 tablets vs. 2 tablets of 5 mg oxycodone, p < .001). The majority of patients reported receiving education on taking opioids, but only 27% received instructions on proper disposal; 82% of prescriptions filled resulted in unused opioids, and only 11% of these patients safely disposed of them. CONCLUSIONS: This study demonstrates that opioid prescribing exceeds consumption following common surgical oncology procedures, indicating the potential for reductions in prescribing.

A randomised trial of bilateral erector spinae plane block vs. no block for thoracolumbar decompressive spinal surgery.

Major spinal surgery causes significant postoperative pain. We tested the efficacy and safety of bilateral erector spinae block on quality of recovery and pain after thoracolumbar decompression. We randomly allocated 60 adults to standard care or erector spinae block. Erector spinae block improved the mean (SD) quality of recovery-15 score at 24 postoperative hours, from 119 (20) to 132 (14), an increase (95%CI) of 13 (4-22), p = 0.0044. Median (IQR [range]) comprehensive complication index was 1 (0-3 [0-5]) in the control group vs. 1 (0-1 [0-4]) after block, p = 0.4. Erector spinae block reduced mean (SD) area under the curve pain during the first 24 postoperative hours: at rest, from 78 (49) to 50 (39), p = 0.018; and on sitting, from 125 (51) to 91 (50), p = 0.009. The cumulative mean (SD) oxycodone consumption to 24 h was 27 (18) mg in the control group and 19 (26) mg after block, p = 0.20. In conclusion, erector spinae block improved recovery and reduced pain for 24 h after thoracolumbar decompression surgery.

Impact of the pericapsular nerve group (PENG) block on postoperative analgesia and functional recovery following total hip arthroplasty: a randomised, observer-masked, controlled trial.

The pericapsular nerve group (PENG) block is a novel regional anaesthesia technique that aims to provide hip analgesia with preservation of motor function, although evidence is currently lacking. In this single-centre, observer-masked, randomised controlled trial, patients undergoing total hip arthroplasty received pericapsular nerve group block or no block (control group). Primary outcome measure was maximum pain scores (0-10 numeric rating scale) measured in the first 48 h after surgery. Secondary outcomes included postoperative opioid consumption; patient mobilisation assessments; and length of hospital stay. Sixty patients were randomly allocated equally between groups. The maximum pain score of patients receiving the pericapsular nerve group block was significantly lower than in the control group at all time-points, with a median (IQR [range]) of 2.5 (2.0-3.7 [0-7]) vs. 5.5 (5.0-7.0 [2-8]) at 12 h; 3 (2.0-4.0 [0-7]) vs. 6 (5.0-6.0 [2-8]) at 24 h; and 2.0 (2.0-4.0 [0-5]) vs. 3.0 (2.0-4.7 [0-6]) at 48 h; all p < 0.001. Moreover, the pericapsular nerve group showed a significant reduction in opioid consumption, better range of hip motion and shorter time to ambulation. Although no significant difference in hospital length of stay was detected, our results suggest improved postoperative functional recovery following total hip arthroplasty in patients who received pericapsular nerve group block.

Intra-articular infiltration analgesia for arthroscopic shoulder surgery: a systematic review and meta-analysis.

Phrenic-sparing analgesic techniques for shoulder surgery are desirable. Intra-articular infiltration analgesia is one promising phrenic-sparing modality, but its role remains unclear because of conflicting evidence of analgesic efficacy and theoretical concerns regarding chondrotoxicity. This systematic review and meta-analysis evaluated the benefits and risks of intra-articular infiltration in arthroscopic shoulder surgery compared with systemic analgesia or interscalene brachial plexus block. We sought randomised controlled trials comparing intra-articular infiltration with interscalene brachial plexus block or systemic analgesia (control). Cumulative 24-h postoperative oral morphine equivalent consumption was designated as the primary outcome. Secondary outcomes included visual analogue scale pain scores during the first 24 h postoperatively; time-to-first analgesic request; patient satisfaction; opioid-related side-effects; block-related adverse events; and any indicators of chondrotoxicity. Fifteen trials (863 patients) were included. Compared with control, intra-articular infiltration reduced 24-h postoperative analgesic consumption by a weighted mean difference (95%CI) of -30.9 ([-38.9 to -22.9]; p < 0.001). Intra-articular infiltration also reduced the weighted mean difference (95%CI) pain scores up to 12 h postoperatively, with the greatest reduction at 4 h (-2.2 cm [(-4.4 to -0.04]); p < 0.05). Compared with interscalene brachial plexus block, there was no difference in opioid consumption, but patients receiving interscalene brachial plexus block had better pain scores at 2, 4 and 24 h postoperatively. There was no difference in opioid- or block-related adverse events, and none of the trials reported chondrotoxic effects. Compared with systemic analgesia, intra-articular infiltration provides superior pain control, reduces opioid consumption and enhances patient satisfaction, but it may be inferior to interscalene brachial plexus block patients having arthroscopic shoulder surgery.

Temporomandibular joint dysfunction following the use of a supraglottic airway device during general anaesthesia: a prospective observational study.

Supraglottic airway devices are commonly used to manage the airway during general anaesthesia. There are sporadic case reports of temporomandibular joint dysfunction and dislocation following supraglottic airway device use. We conducted a prospective observational study of adult patients undergoing elective surgery where a supraglottic airway device was used as the primary airway device. Pre-operatively, all participants were asked to complete a questionnaire involving 12 points adapted from the Temporomandibular Joint Scale and the Liverpool Oral Rehabilitation Questionnaire. Objective measurements included inter-incisor distance as well as forward and lateral jaw movements. The primary outcome was the inter-incisor distance, an accepted measure of temporomandibular joint mobility. Both the questionnaire and measurements were repeated in the postoperative period and we analysed data from 130 participants. Mean (SD) inter-incisor distance in the pre- and postoperative period was 46.5 (7.2) mm and 46.3 (7.5) mm, respectively (p = 0.521) with a difference (95%CI) of 0.2 (-0.5 to 0.9) mm. Mean (SD) forward jaw movement in the pre- and postoperative period was 3.6 (2.4) mm and 3.9 (2.4) mm, respectively (p = 0.018). Mean (SD) lateral jaw movement to the right in the pre- and postoperative period was 8.9 (4.1) mm and 9.1 (4.0) mm, respectively (p = 0.314). Mean (SD) lateral jaw movement to the left in the pre- and postoperative period was 8.8 (4.0) mm and 9.3 (3.6) mm, respectively (p = 0.008). The number of patients who reported jaw clicks or pops before opening their mouth as wide as possible was 28 (21.5%) vs. 12 (9.2%) in the pre- and postoperative period, respectively (p < 0.001) with a difference (95%CI) of 12.3% (6.7-17.9%). There was no significant difference in the responses to the other 11 questions or in the number of patients who reported pain in the temporomandibular joint area postoperatively. No clinically significant dysfunction of the temporomandibular joint following the use of supraglottic airway devices in the postoperative period was identified by either patient questionnaires or objective measurements.

Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury.

Autotomy, self-mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to investigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macrophage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macrophages were concentrated around NF200-labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macrophages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy.

Persistent proliferation of keratinocytes and prolonged expression of pronociceptive inflammatory mediators might be associated with the postoperative pain in KK mice.

Epidermal keratinocytes play a vital role in restoration of the intact skin barrier during wound healing. The negative effect of hyperglycemia may prolong the wound healing process. Epidermal keratinocytes have been demonstrated to modulate and directly initiate nociceptive responses in rat models of fractures and chemotherapy-induced neuropathic pain. However, it is unclear whether epidermal keratinocytes are involved in the development and maintenance of incisional pain in nondiabetic or diabetic animals. In the current study, using behavioral tests and immunohistochemistry, we investigated the differential keratinocytes proliferation and expression of pronociceptive inflammatory mediators in keratinocytes in C57BL/6J mice and diabetic KK mice. Our data showed that plantar incision induced postoperative pain hypersensitivity in both C57BL/6J mice and KK mice, while the duration of postoperative pain hypersensitivity in KK mice was longer than that in C57BL/6J mice. Moreover, plantar incision induced the keratinocytes proliferation and expression of IL-1ß and TNF-α in keratinocytes in both C57BL/6J mice and KK mice. Interestingly, compared to C57BL/6J mice, the slower and more persistent proliferation of keratinocytes and expression of IL-1ß and TNF-α in keratinocytes were observed in KK mice. Together, our study suggested that plantar incision may induce the differential keratinocytes proliferation and expression of IL-1ß and TNF-α in kertinocytes in diabetic and nondiabetic animals, which might be associated with the development and maintenance differences in diabetic and nondiabetic postoperative pain.

Opioid Use after Breast-Conserving Surgery: Prospective Evaluation of Risk Factors for High Opioid Use.

BACKGROUND: Responsible opioid prescribing for postoperative pain control is critical. We sought to identify both patient and surgical factors associated with increased opioid use after breast-conserving surgery (BCS). METHODS: Patients (N = 316) undergoing BCS were surveyed to determine postoperative opioid use. Univariate and multivariate analyses were used to determine factors contributing to increased opioid use (highest quartile of use). All opioid prescriptions were converted to oral morphine equivalents (OME) for analysis. RESULTS: The mean opioid prescription was 33.2 OMEs. Fourteen patients (4.4%) did not receive a narcotic prescription at discharge. Seventy-eight patients (24.7%) did not take any opioids after discharge. Those in the highest quartile of use consumed more than 50 OMEs. Surgical factors, such as bilateral oncoplastic surgery (60.8 OMEs vs. 33.1 OMEs, p = 0.0001), axillary lymph node dissection (ALND) (61.5 vs. 30.5, p = 0.0003), and drain use (2 drains 71.1, 1 drain 40.4, no drains 26.2, p = 0.0001), were associated with higher opioid use. In a multivariate analysis, smoking, preoperative opioid use, bilateral oncoplastic surgery, high postoperative reported pain score, placement of at least one surgical drain, and receiving a discharge prescription greater than 150 OMEs were associated with the highest quartile of opioid use. CONCLUSIONS: Smoking, preoperative opioid use, bilateral oncoplastic surgery, ALND, use of surgical drains, high reported postoperative pain score, and receiving a higher OME discharge prescription are associated with higher postoperative opioid use. Given the wide variability of analgesic needs, these criteria should be used to guide the appropriate tailoring of opioid prescriptions.

Paravertebral catheter versus EPidural analgesia in Minimally invasive Esophageal resectioN: a randomized controlled multicenter trial (PEPMEN trial).

BACKGROUND: Thoracic epidural analgesia is the standard postoperative pain management strategy in esophageal cancer surgery. However, paravertebral block analgesia may achieve comparable pain control while inducing less side effects, which may be beneficial for postoperative recovery. This study primarily aims to compare the postoperative quality of recovery between paravertebral catheter versus thoracic epidural analgesia in patients undergoing minimally invasive esophagectomy. METHODS: This study represents a randomized controlled superiority trial. A total of 192 patients will be randomized in 4 Dutch high-volume centers for esophageal cancer surgery. Patients are eligible for inclusion if they are at least 18 years old, able to provide written informed consent and complete questionnaires in Dutch, scheduled to undergo minimally invasive esophagectomy with two-field lymphadenectomy and an intrathoracic anastomosis, and have no contra-indications to either epidural or paravertebral analgesia. The primary outcome is the quality of postoperative recovery, as measured by the Quality of Recovery-40 (QoR-40) questionnaire on the morning of postoperative day 3. Secondary outcomes include the QoR-40 questionnaire score Area Under the Curve on postoperative days 1-3, the integrated pain and systemic opioid score and patient satisfaction and pain experience according to the International Pain Outcomes (IPO) questionnaire, and cost-effectiveness. Furthermore, the groups will be compared regarding the need for additional rescue medication on postoperative days 0-3, technical failure of the pain treatment, duration of anesthesia, duration of surgery, total postoperative fluid administration day 0-3, postoperative vasopressor and inotrope use, length of urinary catheter use, length of hospital stay, postoperative complications, chronic pain at six months after surgery, and other adverse effects. DISCUSSION: In this study, it is hypothesized that paravertebral analgesia achieves comparable pain control while causing less side-effects such as hypotension when compared to epidural analgesia, leading to shorter postoperative length of stay on a monitored ward and superior quality of recovery. If this hypothesis is confirmed, the results of this study can be used to update the relevant guidelines on postoperative pain management for patients undergoing minimally invasive esophagectomy. TRIAL REGISTRATION: Netherlands Trial Registry, NL8037. Registered 19 September 2019.

Perceptions of opioid use and prescribing habits in oncologic surgery: A survey of the society of surgical oncology membership.

BACKGROUND: The objective of this study was to assess current perceptions surrounding opioid prescribing in surgical oncology to inform perioperative quality improvement initiatives. METHODS: After the Society of Surgical Oncology (SSO) approval, a survey was distributed to its membership. Five sample procedures were used to assess provider perceptions and prescribing habits. Data were summarized and compared by self-reported demographics. RESULTS: One hundred and seventy-five participants completed the survey: 149 (85%) faculty, 24 (14%) trainees, and 2 (1%) advanced practice providers. Most participants (76%) practiced in academic programs and 21% practiced in non-US locations. Few differences were identified based on clinical role, academic rank, or practice years. Compared with non-US providers, US providers expected higher pain scores at discharge, recommended greater opioid prescriptions, and estimated more days of opioid use for almost every procedure. More non-US providers believed discharge opioids should not be distributed to patients who are opioid-free in their last 24 inpatient hours (80% vs 50%, P = .001). All providers ranked education as "very important" for reducing opioid prescriptions. CONCLUSIONS: Compared with their international counterparts, US surgical oncology providers expected greater opioid needs and recommended higher prescription numbers. Educating providers on multimodal opioid-sparing bundles, accelerated weaning protocols, and standardized discharge prescribing habits could have a positive impact the US opioid epidemic.

Intraoperative Ketorolac Use Does Not Increase the Risk of Bleeding in Breast Surgery.

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs is an effective adjunct in managing perioperative pain. We sought to determine if the use of intraoperative ketorolac as part of a multimodal ERAS protocol increased the risk of bleeding complications in breast surgery. METHODS: A subset analysis of a prospective cohort study including patients undergoing lumpectomy and mastectomy compared two groups: those who received intraoperative ketorolac and those who did not. Bleeding complications were compared using Fisher's exact test or t test, and analyzed with respect to surgical modality. Patients undergoing immediate reconstruction were excluded. RESULTS: Seven hundred and fifty-eight breast surgeries were performed in a 13-month period: 157 lumpectomy patients and 57 mastectomy patients met inclusion criteria between July 2017 and August 2018. Two hundred and fourteen patients were included in the analysis: 115 received ketorolac and 99 did not. The two groups were similar with regards to sex, age, race, tobacco use, and comorbidities. When analyzed together, there was no difference in bleeding complications between the group that received intraoperative ketorolac and those who did not (2% vs. 2.6%, p = 1.00). No hematomas occurred in the lumpectomy patients, and three occurred in mastectomy patients: one of which received ketorolac, and two did not (5.9% vs. 5.0%, p = 0.575). The rates of seroma, infection, or dehiscence were not significantly different between the two groups, regardless of surgical modality. CONCLUSIONS: The use of intraoperative ketorolac is a useful adjunct in perioperative pain management in breast surgery and does not increase the risk of bleeding.

Paracetamol-Galactose Conjugate: A Novel Prodrug for an Old Analgesic Drug.

Paracetamol has been one of the most commonly used and prescribed analgesic drugs for more than a hundred years. Despite being generally well tolerated, it can result in high liver toxicity when administered in specific conditions, such as overdose, or in vulnerable individuals. We have synthesized and characterized a paracetamol galactosylated prodrug (PARgal) with the aim of improving both the pharmacodynamic and pharmacological profile of paracetamol. PARgal shows a range of physicochemical properties, solubility, lipophilicity, and chemical stability at differing physiological pH values and in human serum. PARgal could still be preclinically detected 2 h after administration, meaning that it displays reduced hepatic metabolism compared to paracetamol. In overdose conditions, PARgal has not shown any cytotoxic effect in in vitro analyses performed on human liver cells. Furthermore, when tested in an animal pain model, PARgal demonstrated a sustained analgesic effect up to the 12th hour after oral administration. These findings support the use of galactose as a suitable carrier in the development of prodrugs for analgesic treatment.

A 96-hour continuous wound infiltration with ropivacaine reduces analgesic consumption after liver resection: A randomized, double-blind, controlled trial.

BACKGROUND: Continuous wound infiltration (CWI) with local anesthetics to reduce morphine consumption in postoperative pain management after open liver resection in patients with cancer. METHODS: This single-center randomized double-blind study allocated patients requiring resection of liver metastases to receive a 3.75 mg/mL ropivacaine (ROP) infiltration, followed by a 2 mg/mL ROP CWI, or placebo (P) for 96 hours. Postoperative analgesia included acetaminophen and patient-controlled analgesia morphine pump. The primary endpoint was to investigate the reduction of total morphine consumption (mg/kg) over the first 96 postoperative hours. RESULTS: Eighty-five patients were recruited, and randomized (ROP: 42, P: 43) between 2009 and 2014. The median morphine consumption significantly decreased in the ROP arm in the first 96 postoperative hours (ROP: 1.0, P: 1.5 mg/kg; P = 0.026). Twenty-three (27%) patients had grade 3 adverse events (ROP: 14, P: 9) and four experienced grade 3 treatment-related adverse events (ROP: mental confusion [n = 1], hallucinations [n = 2], P: hematoma [n = 1]). Two (5%) patients showed a wound inflammation (ROP: 1, P: 1). Nine (11%) patients experienced at least one serious adverse event (ROP: 6, P: 3); none related to treatment. CONCLUSION: Preperitoneal CWI of 2 mg/mL ROP significantly reduces intravenous morphine consumption during the 96 postoperative hours resulting in an absolute reduction of 0.5 mg/kg.

Pain and opioid prescriptions vary by procedure after breast surgery.

BACKGROUND: With the opioid epidemic in the United States, evaluating opioid prescribing patterns is essential. We evaluated opioids prescribed at discharge following breast surgery and their association with patient factors and pain scores. METHODS: We retrospectively identified adult patients who underwent a mastectomy for cancer at Mayo Clinic sites from January 2010 to December 2016. Pain scores and prescription data were compared across operations and patient factors by univariate and multivariable analyses. RESULTS: Of 4021 patients, 3782 (94.1%) received an opioid prescription. Median oral milligram morphine equivalents (MME) were similar across all site-specific procedure groups (medians ranging from 225 to 375) while pain scores ranged from 1 to 4. Patients undergoing bilateral mastectomy (BM) and immediate breast reconstruction (IBR) reported the greatest pain scores. Pain scores did not vary with age or diagnosis for patients undergoing unilateral mastectomy or BM with lymph node surgery and IBR procedures. On multivariable analysis, variables associated with a MME discharge prescription >Q4 values included age, body mass index, site, year, inpatient status, and pain before discharge >3. CONCLUSION: Patient-reported pain following breast surgery varied by procedure, while MMEs prescribed remained similar. This suggests current opioid prescribing does not reflect intensity of pain and requires further research to optimize discharge opioid prescribing practices.

Dural and pial pain-sensitive structures in humans: new inputs from awake craniotomies.

Our knowledge on intracranial pain-sensitive structures in humans comes essentially from observations during neurosurgical procedures performed in awake patients. It is currently accepted that intracranial pain-sensitive structures are limited to the dura mater and its feeding vessels and that small cerebral vessels and pia mater are insensitive to pain, which is inconsistent with some neurosurgical observations during awake craniotomy procedures. We prospectively collected observations of painful events evoked by mechanical stimulation (touching, stretching, pressure, or aspiration) of intracranial structures during awake craniotomies, routinely performed for intraoperative functional mapping to tailor brain tumour resection in the eloquent area. Intraoperatively, data concerning the locations of pain-sensitive structures were drawn by the surgeon on a template and their corresponding referred pain was indicated by the patient by drawing a cross on a diagram representing the head. Ninety-three painful events were observed and collected in 53 different patients (mean age 41.2 years, 25 males) operated on awake craniotomy for left (44 cases) or right (nine cases) supra-tentorial tumour resection in eloquent areas. On average, 1.8 painful events were observed per patient (range 1-5). All the painful events were referred ipsilaterally to the stimulus. In all cases, the evoked pain was sharp, intense and brief, stopped immediately after termination of the causing action, and did not interfere with the continuation of the surgery. In 30 events, pain was induced by stimulation of the dura mater of the skull base (23 events) or of the falx (seven events) and was referred predominantly in the V1 territory and in the temporal region. In 61 cases, pain was elicited by mechanical stimulation of the pia mater or small cerebral vessels of the temporal (19 events), frontal (25 events), parietal (four events) lobes and/or the peri-sylvian region, including the insular lobe (13 events), and referred in the V1 territory. In this observational study, we confirmed that dura of the skull base and dura of the falx cerebri are sensitive to pain and that their mechanical stimulation induced pain mainly referred in the sensory territories of the V1 and V3 divisions of the trigeminal nerve. Unlike earlier studies, we observed that the pia and the small cerebral vessels were also pain-sensitive, as their mechanical stimulation induced pain referred mainly in the V1 territory. These observations suggest that small pial cerebral vessels may also be involved in the pathophysiology of primary and secondary headaches.awy005media15756834882001.

Evaluation of postoperative pain intensity following occlusal reduction in teeth associated with symptomatic irreversible pulpitis and symptomatic apical periodontitis: a randomized clinical study.

AIM: To assess the effect of occlusal reduction on postoperative pain following two visits root canal treatment in posterior mandibular teeth with symptomatic irreversible pulpitis and symptomatic apical periodontitis in a randomized clinical trial. METHODOLOGY: This trial was conducted in the outpatient clinic of the Endodontic Department of the Faculty of Oral and Dental Medicine, Cairo University in Egypt. Forty-four-patients diagnosed with symptomatic irreversible pulpitis and symptomatic apical periodontitis were randomly assigned into two equal groups. The occlusal surfaces of teeth in the intervention group were reduced; whilst those assigned to the control group were left intact. Canal instrumentation was completed in the first visit using Revo-S rotary nickel-titanium files, and pain intensity was assessed using a visual analogue scale (VAS) at 6, 12, 24 and 48 h. Canal filling was completed 7 days later, and pain intensity was assessed at 6 and 12 h. A placebo was given and analgesics were prescribed to be administered in case of severe postoperative pain. Data were analysed using Independent t-test, chi-square and Fisher Exact tests. RESULTS: The mean pain scores within the two groups were associated with a significant continuous decrease over time. Following both instrumentation and canal filling, the mean pain scores in the intervention group were lower than those in the control group at all follow-up periods and this difference was only significant at 12 h (P = 0.021 and P = 0.015, respectively). CONCLUSIONS: Occlusal reduction reduced levels of postoperative pain in posterior mandibular teeth with symptomatic pulpitis and apical periodontitis only 12 h following both canal preparation and root filling.

Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview.

Unlike fever, which is often over-treated especially in children, pain is underestimated and under-treated in pediatric age. The pharmacological agents approved for treating pain in these patients are few, also considering the recent limitation for codeine in children younger than 12 years. Paracetamol and the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen are the most used at this purpose. The aim of this overview was to analyze the therapeutic appropriateness of ibuprofen in children based on its pharmacological properties. This work is a critical review of the pediatric literature over the last 20 years on efficacy and adverse events associated with the use of ibuprofen as analgesic in the pediatric population. Ibuprofen resulted effective in several pain conditions in children such as musculoskeletal pain, ear pain and acute otitis media, toothache and the inflammatory disease of the oral cavity and pharynx. The drug is a reasonable and efficacious alternative in postoperative pain, including tonsillectomy and adenoidectomy. It remains the treatment of choice for pain in chronic inflammatory diseases such as arthritis. Side effects and adverse events associated with ibuprofen are mild. It has the lowest gastrointestinal (GI) toxicity among NSAIDs, although some cases of GI toxicity may occur. Its renal effects are minimal, but dehydration plays an important role in triggering renal damage, so ibuprofen should not be given to patients with vomiting and diarrhea. Ibuprofen showed a good safety profile and provided evidence of effectiveness for mild-moderate pain of different origin in children. In case of fever or pain, the choice about the drug to be used should fall on ibuprofen in a clinical context where there is an inflammatory pathogenesis.

TLR4/NF-κB signaling activation in plantar tissue and dorsal root ganglion involves in the development of postoperative pain.

Background Severe postoperative pain remains a clinical problem that impacts patient's rehabilitation. The present work aims to investigate the role of Toll-like receptor-4 (TLR4) activation in wounded plantar tissue and dorsal root ganglion (DRG) in the genesis of postoperative pain and its underlying mechanisms. Results Postoperative pain was induced by plantar incision in rat hind paw. Plantar incision led to increased expression of TLR4 in ipsilateral lumbar 4-5 (L4/L5) DRGs, which occurred at 2 h and was persistent to the third day after surgery. Similar to the change in TLR4 expression, there was also significant increase in phosphorylated nuclear factor-kappa B p65 (p-p65) in DRGs after surgery. Immunofluorescence staining revealed that the increased expressions of TLR4 and p-p65 not only in neuronal cells but also in satellite glial cells in DRG. Furthermore, the enhanced expressions of TLR4 and p-p65 were also detected in plantar tissues around the incision, which was observed starting at 2 h and lasting until the third day after surgery. Prior intrathecal (i.t.) injections of TAK-242 (a TLR4-specific antagonist) or 4',6-diamidino-2-phenylindole-dihydrochloride (PDTC, a nuclear factor-kappa B activation inhibitor) dose dependently alleviated plantar incision-induced mechanical allodynia and thermal hyperalgesia and inhibited the increased expressions of p-p65, tumor necrosis factor-alpha, and interleukin-1 beta in DRG. Prior subcutaneous (s.c.) plantar injection of TAK-242 or PDTC also ameliorated pain-related hypersensitivity following plantar incision. Moreover, the plantar s.c. injection of TAK-242 or PDTC inhibited the increased expressions of p-p65, tumor necrosis factor-alpha, and interleukin-1 beta not only in local wounded plantar tissue but also dramatically in ipsilateral lumbar 4-5 DRGs. Conclusion TLR4/ nuclear factor-kappa B signaling activation in local injured tissue and DRG contribute to the development of postoperative pain via regulating pro-inflammatory cytokines release. Targeting TLR4/ nuclear factor-kappa B signaling in local tissue at early stage of surgery may be an effective strategy for the treatment of postoperative pain.