INTRODUCTION: This systematic review evaluated the use of buffered versus non-buffered lidocaine to increase the efficacy of inferior alveolar nerve block (IANB). MATERIALS AND METHODS: Randomized, double-blinded studies from PubMed, Web of Science, Cochrane Library, Embase, and ProQuest were identified. Two of the authors assessed the studies for risk of bias. Outcomes included onset time, injection pain on a visual analog scale (VAS), percentage of painless injections, and anesthetic success rate of IANB. RESULTS: The search strategy yielded 19 references. Eleven could be included in meta-analyses. Risk of bias was unclear in ten and high in one study. Buffered lidocaine showed 48 seconds faster onset time (95% confidence interval [CI], −42.06 to −54.40; P < 0.001) and 5.0 units lower (on a scale 0–100) VAS injection pain (95% CI, −9.13 to −0.77; P=0.02) than non-buffered. No significant difference was found on percentage of people with painless injection (P = 0.059), nor success rate (P = 0.290). CONCLUSION: Buffered lidocaine significantly decreased onset time and injection pain (VAS) compared with non-buffered lidocaine in IANB. However due to statistical heterogeneity and low sample size, quality of the evidence was low to moderate, additional studies with larger numbers of participants and low risk of bias are needed to confirm these results.
Bias (Epidemiology) ; Epinephrine ; Lidocaine ; Mandibular Nerve ; Population Characteristics ; Sample Size ; Sodium Bicarbonate ; Sodium ; Visual Analog Scale

This systematic review aimed to analyze the efficacy of corticosteroid premedication compared to placebo or no treatment to reduce postoperative pain in endodontic patients. Randomized controlled trials (RCTs) assessing corticosteroids via oral, intramuscular, subperiosteal, intraligamentary or intracanal route compared to passive or active placebo, or no treatment were included. Four databases were searched: PubMed, Web of Science, Cochrane Library and Embase up to 2/21/2018. Risk of bias was assessed with Cochrane Risk of bias tool. Fourteen RCTs with 1,462 generally healthy adults in need of endodontic treatment were included. 50% of the studies were at unclear risk and 50% at high risk of bias. Meta-analysis showed Visual Analog Scale (VAS) pain at 4–6 hours after Inferior Alveolar Nerve Block (IANB) was significantly lower by 21 points (0–100 scale) in the corticosteroid group compared to the control group (95% CI −35 to −7; P = 0.003), however this difference was not statistically significant after 24 hours (P = 0.116). The route of administration was oral and intraligament injection. Patients who received corticosteroids prior to IANB were 70.7% more likely to have none or mild pain 4–8 hours after treatment (P = 0.001) and 13.5% more likely 24 hours after IANB (P = 0.013) than patients in the control group. In conclusion, corticosteroid administration (oral or intraligamental) may clinically reduce the level of postoperative pain at 4–8 hours after IANB, however the quality of the evidence was low/moderate due to risk of bias and heterogeneity. Further studies are recommended.
Adrenal Cortex Hormones ; Adult ; Bias (Epidemiology) ; Humans ; Mandibular Nerve ; Pain, Postoperative ; Population Characteristics ; Premedication ; Visual Analog Scale

Background: Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of productivity on a global scale. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of ketamine on migraines and other primary headache disorders compared to placebo and other active interventions, such as midazolam, metoclopramide/diphenhydramine, and prochlorperazine/diphenhydramine. Methods: An electronic search of databases published up to February 2021, including Medline via PubMed, EMBASE, Web of Science, and Cochrane Library, a hand search of the bibliographies of the included studies, as well as literature and systematic reviews found through the search was conducted to identify randomized controlled trials (RCTs) investigating ketamine in the treatment of migraine/headache disorders compared to the placebo. The authors assessed the risk of bias according to the Cochrane Handbook guidelines. Results: The initial search strategy yielded 398 unduplicated references, which were independently assessed by three review authors. After evaluation, this number was reduced to five RCTs (two unclear risk of bias and three high risk of bias). The total number of patients in all the studies was 193. Due to the high risk of bias, small sample size, heterogeneity of the outcomes reported, and heterogeneity of the comparison groups, the quality of the evidence was very low. One RCT reported that intranasal ketamine was superior to intranasal midazolam in improving the aura attack severity, but not duration, while another reported that intranasal ketamine was not superior to metoclopramide and diphenhydramine in reducing the headache severity. In one trial, subcutaneous ketamine was superior to saline in migraine severity reduction; however, intravenous (I.V.) ketamine was inferior to I.V. prochlorperazine and diphenhydramine in another study. Conclusion Further double-blind controlled studies are needed to assess the efficacy of ketamine in treating acute and chronic refractory migraines and other primary headaches using intranasal and subcutaneous routes. These studies should include a long-term follow-up and different ketamine dosages in diagnosed patients following international standards for diagnosing headache/migraine.

Background: Chronic neuropathic pain (NP) presents therapeutic challenges. Interest in the use of cannabis-based medications has outpaced the knowledge of its efficacy and safety in treating NP. The objective of this review was to evaluate the effectiveness of cannabis-based medications in individuals with chronic NP. Methods: Randomized placebo-controlled trials using tetrahydrocannabinol (THC), cannabidiol (CBD), cannabidivarin (CBDV), or synthetic cannabinoids for NP treatment were included. The MEDLINE, Cochrane Library, EMBASE, and Web of Science databases were examined. The primary outcome was the NP intensity. The risk of bias analysis was based on the Cochrane handbook. Results: The search of databases up to 2/1/2021 yielded 379 records with 17 RCTs included (861 patients with NP). Meta-analysis showed that there was a significant reduction in pain intensity for THC/CBD by –6.624 units (P < .001), THC by -8.681 units (P < .001), and dronabinol by -6.0 units (P = .008) compared to placebo on a 0–100 scale. CBD, CBDV, and CT-3 showed no significant differences. Patients taking THC/CBD were 1.756 times more likely to achieve a 30% reduction in pain (P = .008) and 1.422 times more likely to achieve a 50% reduction (P = .37) than placebo. Patients receiving THC had a 21% higher improvement in pain intensity (P = .005) and were 1.855 times more likely to achieve a 30% reduction in pain than placebo (P < .001). Conclusion Although THC and THC/CBD interventions provided a significant improvement in pain intensity and were more likely to provide a 30% reduction in pain, the evidence was of moderate-to-low quality. Further research is needed for CBD, dronabinol, CT-3, and CBDV.

Background: Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of productivity on a global scale. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of ketamine on migraines and other primary headache disorders compared to placebo and other active interventions, such as midazolam, metoclopramide/diphenhydramine, and prochlorperazine/diphenhydramine. Methods: An electronic search of databases published up to February 2021, including Medline via PubMed, EMBASE, Web of Science, and Cochrane Library, a hand search of the bibliographies of the included studies, as well as literature and systematic reviews found through the search was conducted to identify randomized controlled trials (RCTs) investigating ketamine in the treatment of migraine/headache disorders compared to the placebo. The authors assessed the risk of bias according to the Cochrane Handbook guidelines. Results: The initial search strategy yielded 398 unduplicated references, which were independently assessed by three review authors. After evaluation, this number was reduced to five RCTs (two unclear risk of bias and three high risk of bias). The total number of patients in all the studies was 193. Due to the high risk of bias, small sample size, heterogeneity of the outcomes reported, and heterogeneity of the comparison groups, the quality of the evidence was very low. One RCT reported that intranasal ketamine was superior to intranasal midazolam in improving the aura attack severity, but not duration, while another reported that intranasal ketamine was not superior to metoclopramide and diphenhydramine in reducing the headache severity. In one trial, subcutaneous ketamine was superior to saline in migraine severity reduction; however, intravenous (I.V.) ketamine was inferior to I.V. prochlorperazine and diphenhydramine in another study. Conclusion Further double-blind controlled studies are needed to assess the efficacy of ketamine in treating acute and chronic refractory migraines and other primary headaches using intranasal and subcutaneous routes. These studies should include a long-term follow-up and different ketamine dosages in diagnosed patients following international standards for diagnosing headache/migraine.

Trigeminal neuralgia (TN) involves chronic neuropathic pain, characterized by attacks of repeating short episodes of unilateral shock-like pain, which are abrupt in onset and termination. Anticonvulsants, such as carbamazepine, are the gold standard first-line drugs for pharmacological treatment. Microvascular decompression (MVD) surgery is often the course of action if pharmacological management with anticonvulsants is unsuccessful. MVD surgery is an effective therapy in approximately 83% of cases. However, persistent neuropathic pain after MVD surgery may require reintroduction of pharmacotherapy. This case report presents two patients with persistent pain after MVD requiring reintroduction of pharmacological therapy. Although MVD is successful for patients with failed pharmacological management, it is an invasive procedure and requires hospitalization of the patient. About one-third of patients suffer from recurrent TN after MVD. Often, alternative treatment protocols, including the reintroduction of medications, may be necessary to achieve improvement. This case report presents two cases of post-MVD recurrent pain. Further research is lacking on the success rates of subsequent medication therapy after MVD has proven less effective in managing TN.

This systematic review focused on the efficacy of topical products in reducing temporomandibular joint disorder (TMD)-associated pain, in comparison to placebo or control interventions. The EMBASE, Web of Science, Cochrane Library, and MEDLINE via PubMed databases were searched for randomized controlled trials (RCTs) using topical interventions in adults diagnosed with TMD. The pain intensity was the primary outcome, and other clinical findings were the secondary outcomes. The risk of bias was evaluated according to the Cochrane’s handbook. The search up to February 7, 2020 identified a total of 496 unduplicated references. Nine RCTs with 355 adult patients diagnosed with TMD were included. The meta-analysis did not show a significant reduction in baseline pain intensity in the nonsteroidal anti-inflammatory drug (NSAIDs) group, when compared to the placebo group (P = 0.288). One study demonstrated a statistically significant pain score decrease for Theraflex-TMJ compared to placebo after 10 d of treatment (P = 0.003) and follow-up, 5 d after the last application (P = 0.027). Ping On reduced pain at 4 weeks of application (P < 0.001) but not after 7 d of application (P = 0.136). In one study, cannabidiol (CBD) significantly improved the pain intensity compared to placebo (P < 0.001). However, no differences were found with capsaicin in the two studies (P = 0.465). Evidence was of low quality because the studies were considered as having an unclear or a high risk of bias and a small number of studies were analyzed. The evidence is not sufficient to support the use of topical NSAIDs and capsaicin, and limited evidence was found for Threraflex-TMJ, bee venom, Ping On, and CBD, with only one study reporting for each. Additional studies are recommended to validate these results.

This systematic review and meta-analysis aimed to analyze the effectiveness of maxillary stabilization splint (SS) therapy to reduce headache (HA) intensity and HA frequency in patients with temporomandibular disorders (TMD)-HA comorbidity. Randomized controlled trials (RCTs) using full-arch coverage, hard resin, and maxillary SS therapy were included. Electronic databases, including Cochrane Library, MEDLINE through PubMed, Web of Science, and EMBASE, were searched. The risk of bias was analyzed based on Cochrane’s handbook. The search yielded 247 references up to January 28, 2020. Nine RCTs were included at a high risk of bias. The comparison groups included other splints, counseling, jaw exercises, medications, neurologic treatment, and occlusal equilibration. Four studies reported a statistically significant reduction in HA intensity, and five studies reported significant improvement in HA frequency from baseline at 2-12 months in patients with TMD-HA comorbidity treated with a full-arch hard maxillary SS. HA frequency in tension-type HA (TTH) comorbid with TMD diagnoses of myofascial pain (MFP) or capsulitis/synovitis improved significantly with SS than that with full-arch maxillary non-occluding splint (NOS) in two studies. Comparison groups receiving hard partial-arch maxillary splint nociceptive trigeminal inhibition (NTI) showed statistically significant improvements in HA intensity in patients with mixed TMD phenotypes of MFP and disc displacement comorbid with “general HA.” Comparison groups receiving partial-arch maxillary resilient/soft splint (Relax) showed significant improvements in both HA intensity and frequency in patients with HA concomitant with MFP. The meta-analysis showed no statistically significant difference in the improvement of pain intensity at 2-3 months with comparison of the splints (partial-arch soft [Relax], hard [NTI], and full-arch NOS) or splint use compliance at 6-12 months with comparison of the splints (partial-arch Relax and full-arch NOS) versus the SS groups in patients with various TMD-HA comorbidities. In conclusion, although SS therapy showed a statistically significant decrease in HA intensity and HA frequency when reported, the evidence quality was low due to the high bias risk and small sample size. Therefore, further studies are required.

Background: Trigeminal neuralgia (TN) is characterized by brief, unilateral, sharp, stabbing, and shooting pain of the fifth cranial nerve. The objective of this systematic review with meta-analysis was to determine the effect of medications compared to placebo in adult patients with TN. Methods: Review authors identified randomized placebo-controlled trials (RCTs) from PubMed, Web of Science, Cochrane, and EMBASE up to February 2021. We assessed the inclusion and exclusion criteria as well as the risk of bias of the studies based on the Cochrane Handbook. A total of 324 unduplicated references were scanned independently and reduced to eight relevant RCTs, with 89 patients included. Medications investigated included oral carbamazepine, subcutaneous sumatriptan, lidocaine (intranasal, 8% spray on the oral mucosa or intravenous), buprenorphine (ganglionic local opioid analgesia), and oral Nav1.7, a selective sodium channel blocker. Results: Meta-analyses showed that overall patients receiving lidocaine reported a significantly lower post-treatment intensity of pain −3.8 points on a 0–10 scale (95% Cl = −4.653 to −2.873; P < 0.001). Patients who received lidocaine were 8.62 times more likely to have pain improvement than patients on placebo (P < 0.001). In one RCT, patients receiving oral carbamazepine showed a significant improvement in pain intensity of −32% compared to the placebo (P < 0.001). In one trial, patients receiving 3 mg subcutaneous sumatriptan had a significantly lower intensity of pain on average −6.1 points on a scale of 0–10 compared to placebo (P < 0.001) and a significant improvement in pain intensity of −75% compared to the improvement in the placebo group (P < 0.001). Patients who received subcutaneous sumatriptan were 10 times more likely to have pain improvement than those who received placebo (P = 0.001) in one study. Due to the unclear/high risk of bias and small sample size, the quality of the evidence for lidocaine in the treatment of TN was low. Conclusion Further studies are needed for carbamazepine, sumatriptan, buprenorphine, and oral Nav1.7 sodium channel blockers, as only one study reported outcomes.

This systematic review and meta-analysis aimed to analyze the effectiveness of maxillary stabilization splint (SS) therapy to reduce headache (HA) intensity and HA frequency in patients with temporomandibular disorders (TMD)-HA comorbidity. Randomized controlled trials (RCTs) using full-arch coverage, hard resin, and maxillary SS therapy were included. Electronic databases, including Cochrane Library, MEDLINE through PubMed, Web of Science, and EMBASE, were searched. The risk of bias was analyzed based on Cochrane’s handbook. The search yielded 247 references up to January 28, 2020. Nine RCTs were included at a high risk of bias. The comparison groups included other splints, counseling, jaw exercises, medications, neurologic treatment, and occlusal equilibration. Four studies reported a statistically significant reduction in HA intensity, and five studies reported significant improvement in HA frequency from baseline at 2-12 months in patients with TMD-HA comorbidity treated with a full-arch hard maxillary SS. HA frequency in tension-type HA (TTH) comorbid with TMD diagnoses of myofascial pain (MFP) or capsulitis/synovitis improved significantly with SS than that with full-arch maxillary non-occluding splint (NOS) in two studies. Comparison groups receiving hard partial-arch maxillary splint nociceptive trigeminal inhibition (NTI) showed statistically significant improvements in HA intensity in patients with mixed TMD phenotypes of MFP and disc displacement comorbid with “general HA.” Comparison groups receiving partial-arch maxillary resilient/soft splint (Relax) showed significant improvements in both HA intensity and frequency in patients with HA concomitant with MFP. The meta-analysis showed no statistically significant difference in the improvement of pain intensity at 2-3 months with comparison of the splints (partial-arch soft [Relax], hard [NTI], and full-arch NOS) or splint use compliance at 6-12 months with comparison of the splints (partial-arch Relax and full-arch NOS) versus the SS groups in patients with various TMD-HA comorbidities. In conclusion, although SS therapy showed a statistically significant decrease in HA intensity and HA frequency when reported, the evidence quality was low due to the high bias risk and small sample size. Therefore, further studies are required.