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Blackwell Publishing IncMalden, USAPPRPain Practice1530-70852006 World Institute of Pain2006628995Original ArticleOccipital Nerve Blockade for Cervicogenic HeadacheNAJA ET AL. ORIGINAL ARTICLE Occipital Nerve Blockade for Cervicogenic Headache: A DoubleBlind Randomized Controlled Clinical Trial Zoher M. Naja, MD*; Mariam El-Rajab, MD†; Mohamad A. Al-Tannir, MPH‡; Fouad M. Ziade, PhD§; Omar M. Tawfik, MD¶ *Chairman of Anesthesia Department, Makassed General Hospital; †Department of Pediatrics, Makassed General Hospital; ‡Research Unit at Makassed General Hospital; §Faculty of Public Health, Lebanese University, Beirut, Lebanon; ¶Faculty of Medicine, National Cancer Institute, Cairo University, Egypt Abstract: Cervicogenic headache is a chronic hemicranial pain, usually occurring daily. This randomized, double-blind, placebo-controlled trial evaluated the effectiveness of nerve stimulator-guided occipital nerve blockade in the treatment of cervicogenic headache. The reduction in analgesic consumption was the primary outcome measure. Fifty adult patients diagnosed with cervicogenic headache were randomly divided into two equal groups of 25 patients each. All patients in both groups received greater and lesser occipital blocks, whereas only 16 patients in each group received facial nerve blockade in association with the occipital blocks. The control group received injections of an equivalent volume of preservative-free normal saline. Pain was assessed using the visual analog scale (VAS) and the Total Pain Index (TPI). Fortyseven patients entered into the final analysis as three patients were lost to follow-up. Anesthetic block was effective in reducing the VAS and the TPI by approximately 50% Address correspondence and reprint requests to: Zoher M. Naja, MD, Chairman of Anaesthesia Department, Makassed General Hospital, P.O. Box: 11-6301 Riad El-Solh 11072210, Beirut, Lebanon. E-mail: [email protected]. The work was conducted at the Department of Anesthesia at Makassed General Hospital. All funding sources were departmental. Submitted: October 19, 2005; Revision received: December 9, 2005; Final revision accepted: February 7, 2006 © 2006 World Institute of Pain, 1530-7085/06/$15.00 Pain Practice, Volume 6, Issue 2, 2006 89–95 from baseline values (P = 0.0001). Analgesic consumption, duration of headache and its frequency, nausea, vomiting, photophobia, phonophobia, decreased appetite, and limitations in functional activities were significantly less in block group compared to control group (P < 0.05). The nerve stimulator-guided occipital nerve blockade significantly relieved cervicogenic headache and associated symptoms at two weeks following injection. Key Words: occipital blockade, cervicogenic headache, nerve stimulation INTRODUCTION Cervicogenic headache (CGH) is a chronic hemicranial pain usually beginning in the suboccipital region and spreading anteriorly to the ipsilateral orbital, frontal, and temporal areas. This headache, of almost daily occurrence, is typically dominant on one side, but may occasionally be bilateral.1,2 It has been proposed that the mechanism responsible for this headache is related to the convergence of upper cervical and trigeminal sensory pathways allowing pain signals to refer from the neck to the trigeminal sensory receptive fields of the head and face.3–5 Greater occipital nerve (GON) and lesser occipital nerve (LON) anesthetic blocks have been reported to be 90 • naja et al. useful in diagnosing CGH and may sometimes provide temporary pain relief.3,4,6,7 Pain management using medication, physical therapy, manipulative treatment, anesthetic, and surgical interventions have not consistently provided substantial pain relief and are followed by recurrence of pain.3,8–14 At our institution, nerve stimulator-guided blocks of GON and LON have been used for treatment of CGH since 1998 for pain management. The aim of this study was to assess the efficacy of occipital nerve blocks vs. placebo injection using a nerve stimulator in the treatment of CGH. MATERIALS AND METHODS Study Design and Population Following institutional Research and Ethics Committee approval, informed consent was obtained from 50 adult patients diagnosed with CGH for participation in this randomized, double-blind, placebo-controlled study. The diagnosis of CGH was based on all of the following inclusion criteria: unilateral, without sideshift, headache; precipitation of headache by neck movement or by external pressure over the GON; reduced range of motion in the neck; circumscribed tenderness over the GON; and sensory changes in the distribution of the GON. Patients with whiplash injury, post-traumatic headache receiving concurrent psychiatric therapy, organic disease of the brain or spinal cord, malignancy, or coagulopathy were excluded from the study.15 All patients entered a two-week baseline evaluation period where all patients received the same pain treatments. Patients were then randomly divided into two equal groups of 25 patients each, based on computerized generated tables using the sealed-envelope technique. Data collected for each patient at the initial visit included demographics and history of headache including its duration in years. For baseline assessment, each patient received 14 time charts to record the use of rescue medications, daily pain scores, and accompanying symptoms. The incidence of associated nausea, vomiting, photophobia, phonophobia, decreased appetite, and limited normal activity was reported as present or absent (yes/no). Patients in the anesthetic block group received either both GON and LON blocks, or GON and LON with facial nerve blockade, depending on the extension of the headache. Each 10 mL of the injected mixture contained: 3 mL lidocaine 2% (B/Braun, Melsugen, Germany); 3 mL lidocaine 2% with epinephrine 1:200,000; 2.5 mL bupivacaine 0.5% (Laboratoire Aguettant, Lyon, France); 0.5 mL fentanyl 50 µg/mL (Panpharma, Fougères, France); and 1 mL clonidine 150 µg/mL (Bouhring, Paris, France). And the control group received injections of an equivalent volume of preservative-free normal saline. The institutional drug service performed randomization and preparation of the anesthetic mixture. The study was double-blinded as the operator (responsible for the blocks) and both the patient and the nurse responsible for data collection were blinded to the assigned group and to the contents of the syringe. All patients were informed prior to block performance that slight pain and temporary numbness may occur following the performance of the blocks. Following block performance (anesthetic mixture or normal saline), patients received another 14 daily charts to record the use of rescue medications, the daily pain scores, and the accompanying symptoms. Pain Assessment Pain was assessed using a visual analog scale (VAS) (0 cm––no pain; 10 cm—worst possible pain imagined). Pain was also assessed by using the Total Pain Index (TPI).11 The TPI is an integrated expression of the weighted intensity and duration of the headache attacks during a period of two weeks and defined by the formula: (D1·1) + (D2·2) + (D3·3) where D1 = number of hours with headache during the two-week period with slight pain (not limiting normal activity); D2 = number of hours with headache during the two weeks with moderate pain (limiting normal activity, but not causing the subject to go to bed); and D3 = number of hours of headache during the two weeks where strong pain was reported (limiting all activities and causing the subject to be bedridden). Analgesic Consumption Patients were asked to record the quantity of analgesics needed per day during this trial. Patients with a VAS <4 were given either oral paracetamol 500 mg (Defalgan, UPSA, Paris, France) with a maximum of 6 tablets per 24 h, or ketoprofen 100 mg tablet (Profenid, Aventis, Paris, France) without exceeding 3 tablets per day. Patients with a VAS >4 were given either an oral combination of dextropropoxyphene (30 mg) and paracetamol (400 mg) (Diantalvic, Hoechst-Marion-Roussel, France) with a maximum of 6 capsules/day, or tramadol hydrochloride 100 mg tablet (Tramal, Grünenthal, Occipital Nerve Blockade for Cervicogenic Headache • 91 Aachen, Germany) without exceeding 3 tablets per day. Patients were re-evaluated in the clinic at two weeks. Greater Occipital Nerve Blockade Using the Nerve Stimulator GON blockade was selected for patients having pain in the parietal and occipital areas. Technique: In the sitting position, with the hair held out of the field with an adhesive bandage, the superior nuchal line was defined from the mastoid to the cervical spine at C1–C2. A parallel line to the superior nuchal line located 1 cm below it was drawn to find the optimal injection point to block the GON. Following aseptic preparation of the skin, a 24-G nerve stimulator needle (Stimuplex, B.Braun, Melsungen, Germany) was moved horizontally on the surface of the skin toward the midline in 1-mm increments on the previously drawn line using an initial stimulating current of 2.5 mA (1 Hz, 9 v, duration of voltage current was 1.0 ms) (Stimuplex). The point of injection was defined as the most sensitive point declared by the patient along the line. Prior to insertion of the needle, lidocaine 0.1 mL was infiltrated using a 29-G needle to facilitate the penetration of the nerve stimulator needle, which was then progressively advanced perpendicularly to the skin in all planes. Patient co-operation is required as the report of a tingling sensation must be maintained while reducing current to 0.3 mA, indicating that the tip of the needle was in close proximity to the GON. Three milliliters of local anesthetic mixture or normal saline was then injected. The needle was usually inserted approximately about 2.5 cm below the greater occipital protuberance at a depth that varied from 0.5 to 2.5 cm, depending upon the weight and height of the patient. progressively advanced perpendicular to the skin in all planes. The patient was asked to inform the operator that the sensation was still present while the current was reduced to 0.3 Ma, indicating that the tip of the needle was in the vicinity of LON. Three milliliters of anesthetic mixture or normal saline were then injected. The needle was typically inserted to a depth between 0.5 and 1.5 cm. Facial Nerve Blockade Using the Nerve Stimulator If the patient described pain extending to the orbital area, an injection of 3 mL of anesthetic mixture or normal saline was applied to the facial nerve. The injection site was determined by the guidance of a nerve stimulator as described above and was located at the angle of the mandible corresponding to the lowest edge of the ear while observing the muscle contractions of the orbicularis oculi, in addition to the nasal (depressor septi) and buccolabial musculature (depressor anguli oris) (Figure 1). The depth of needle did not exceed 1 cm. Based upon the initial pain sites recorded by the patient during the two weeks preceding the block performance (baseline), all patients in both groups received both greater and lesser occipital blocks, whereas only 16 patients in each group received the facial blockade in association with the occipital blocks. Statistical Analysis Sample size was based on the primary endpoint of the consumption of paracetamol where a 20% reduction was considered significant. A sample size of 25 patients Lesser Occipital Nerve Blockade Using the Nerve Stimulator The LON blockade was selected for patients having pain extending to the frontal and temporal areas. Technique: After sterile preparation as described above, the tip of the nerve stimulator needle was again moved along the skin surface with the stimulating current of 2.5 mA toward the superior third of the posterior limit of the sternocleidomastoid muscle,16 in order to localize the LON. The injection point was defined as the most sensitive point declared by the patient while feeling the current radiating to the temporal region (Figure 1). Some patients also sensed the current passing to the ear. Skin infiltration with lidocaine 0.1 mL using a 29-G needle was performed. Then the nerve stimulator needle was Injection point of facial nerve Injection point of lesser occipital nerve Sternocleidomastoid muscle Trapezius muscle Figure 1. Injection points for the lesser occipital and facial nerves. 92 • naja et al. per group provided 90% power. The demographic characteristics of the two groups were compared using a t-test for continuous measures and Fisher’s exact test for categorical measures. For the primary endpoint, repeated-measures two-way ANOVA was used to assess differences in cumulative analgesics, accepting a P value of <0.05 as statistically significant. The data were compared using two-sided tests for paired comparisons. RESULTS Forty-seven patients were entered into the final analysis; three patients were lost to follow-up (Figure 2). The two study groups had similar baseline characteristics (Table 1). There was a significant reduction in analgesic consumption in block group compared to placebo group. Paracetamol and dextropropoxyphene consumption were significantly less in block patients compared to placebo patients (P = 0.0001) (Table 2). In addition, the consumption of tramadol and ketoprofen was significantly reduced in block group compared to placebo group (P = 0.006 and P = 0.01, respectively) (Table 2). Two weeks after the injection of the anesthetic mixture, block patients reported nearly a 50% improvement in the TPI and VAS scores compared to basal values and to placebo patients (P = 0.0001) (Table 2). The frequency of headaches was reduced in block group compared to placebo group (P = 0.026) (Table 2). Block patients had significantly reduced accompanying symptoms such as nausea, vomiting, photophobia, phonophobia, decreased appetite, and limiting normal activity compared to control group (P values ranged from 0.045 to 0.012) (Table 2). Two weeks following the intervention, the pain site in block group changed compared to control group, with significant reductions in occipital and frontal symptoms (Table 2). The duration of pain relief after block performance was significantly longer in the block group compared to the placebo group (P = 0.0001) (Table 2). For the block group (n = 24), the mean number of days with pain relief (days prior to need of analgesics after injections) was 3.67 (±1.71 SD), whereas for the control group, the Randomization (n = 50 Patients) mean was 1.52 (±1.20 SD). For those who had combined GON, LON, and facial (n = 16 in each group), there was a significant difference among the mean durations of pain relief (3.93 ± 1.79 SD vs. 1.56 ± 1.26 SD; P = 0.0001). Patients who had anesthetic GON and LON alone (n = 8) had significantly longer duration of pain relief compared to the placebo GON and LON (n = 7), with mean duration of relief of 3.22 (±1.56 SD) and 1.43 (±1.34 SD), respectively (P = 0.029). DISCUSSION CGH remains a major problem as most therapeutic regimes are followed by the recurrence of pain. To date arguably the most effective treatment for CGH is the interruption of pain transmission via the occipital nerves (GON, LON) or their component nerve roots or ganglia, either by means of an anesthetic block or through a surgical intervention.10 Our clinical trial was conducted during a two-week period in order to assess the effectiveness of stimulation-guided occipital blockade in reducing the intensity of pain in CGH patients. The findings of this study confirmed our hypothesis that patients receiving anesthetic blockade had decreased analgesic consumption compared to those receiving placebo in CGH patients. Secondary findings included reduced VAS and TPI scores by early 50% of basal values (P = 0.0001). Moreover, accompanying symptoms such as nausea, vomiting, loss of appetite, and extension of pain site were significantly reduced in block group compared to the placebo group during the two-week period of study. One important factor that might contribute to a prolonged pain-free period (outlasting the expected duration of the analgesics administered) is the ability to detect and block the GON precisely rather than simply infiltrating its general location using a field block technique. Accurate injection is also important diagnostically as false localization might lead to unnecessary surgical transection or other neurolytic procedures.4,6 Hence, the nerve stimulator technique enables the operator to determine the exact location of the nerve, increasing the chance for success. Placebo blockade (n = 25) Loss of follow-up (n = 2) Anesthetic blockade (n = 25) Loss of follow-up (n = 1) 47 patients completed the two-week trial Figure 2. CONSORT: Patients’ randomization and follow-up through the clinical trial. Placebo blockade (n = 23) Anesthetic blockade (n = 24) Occipital Nerve Blockade for Cervicogenic Headache • 93 Table 1. Baseline Patient Characteristics Block Group Number of patients Age Sex Female Male History of headache (years) Pain site Temporal Occipital Parietal Frontal Ocular Frequency of headaches/2 weeks Duration of crises (h) Number of analgesics consumed/2 weeks Paracetamol (tablet 500 mg) Number of patients Dextropropoxyphene (capsule 30 mg) Number of patients Tramadol hydrochloride (tablet 50 mg) Number of patients Ketoprofen (tablet 100 mg) Number of patients Visual analog scale (Maximum score obtained in 2 weeks) Total Pain Index (Total Pain Index in 2 weeks) Accompanied symptoms Nausea Yes No Vomiting Yes No Phonophobia and/or photophobia Yes No Decreased appetite Yes No Limited normal activity Yes No Placebo Group P value 25 46.44 (9.63) 25 47.36 (10.25) 0.745 19 (76%) 6 (24%) 12.52 (9.37) 9 [1–32] 18 (72.0%) 7 (28%) 13.20 (9.75) 9 [1–34] 0.999 18 (72%) 25 (100%) 6 (24%) 16 (64%) 16 (64%) 7.36 (2.67) 8 [3–12] 37.04 (16.75) 35 [12–72] 15 (60%) 22 (88%) 8 (32%) 17 (68%) 16 (64%) 7.48 (2.58) 7 [3–12] 35.16 (17.09) 34 [6–72] 0.55 0.363 0.753 0.999 1 0.873 74.16 (12.83) 76 [40–96] 25 (100%) 40.4 (14.13) 42 [0–60] 24 (96%) 4.80 (4.44) 6 [0–13] 15 (60%) 4.20 (5.07) 0 [0–13] 11 (44%) 6.26 (1.65) 7 [3–8] 358.68 (69.98) 369.5 [198–495] 71.04 (18.79) 76 [22–96] 25 (100%) 37.92 (15.91) 40 [0–60] 23 (92%) 5.52 (4.78) 6 [0–12] 16 (64%) 4.48 (5.45) 0 [0–13] 11 (44%) 6.28 (1.79) 7 [3–9] 352.46 (96.90) 373.5 [143–480] 0.496 0.803 0.696 0.563 0.584 0.852 0.967 0.796 13 (52%) 12 (48%) 13 (52%) 12 (48%) 1 6 (24%) 19 (76%) 8 (32%) 17 (68%) 0.753 13 (52%) 12 (48%) 15 (60%) 10 (40%) 0.776 6 (24%) 19 (76%) 7 (28%) 18 (72%) 0.999 12 (48%) 13 (52%) 14 (56%) 11 (44%) 0.777 Data are reported as mean (SD), median [minimum–maximum], or number (%) as appropriate. P < 0.05 was considered significant. The anesthetic mixture selected has produced excellent long-lasting pain relief in a variety of surgical settings.17–20 This multi-anesthetic mixture plays a role in achieving a pain-free period. Others have reported the use of clonidine for migraine.21,22 The addition of clonidine and opioids to local anesthetic solutions has also been found to prolong the duration of nerve blocks.23–25 The observed period of analgesia following the use of the current mixture of local anesthetics, fen- tanyl, and clonidine may have resulted from a synergistic effect. Clonidine might interact with the immune system, resulting in reduced recruitment of macrophages and lymphocytes at the nerve site and a shift in the proportion of macrophages from the pro-inflammatory to the anti-inflammatory phenotype.26 Many authors consider entrapment of the GON to be one of the major underlying causes of CGH.1,4,7 They theorize that the pathogenesis of CGH involves a dis- 94 • naja et al. Table 2. Comparison Between Block Group and Placebo Group at Two Weeks after Treatment Block Group Number of patients Pain site Temporal Occipital Parietal Frontal Ocular Duration of pain relief (days) Frequency of headaches/2 weeks Duration of crises (hours) Number of analgesics consumed/2 weeks Paracetamol (tablet 500 mg) Number of patients Dextropropoxyphene (capsule 30 mg) Number of patients Tramadol hydrochloride (tablet 50 mg) Number of patients Ketoprofen (tablet 100 mg) Number of patients Visual analog scale (Maximum score obtained in 2 weeks) Total Pain Index (Total Pain Index in 2 weeks) Accompanied symptoms Nausea Yes No Vomiting Yes No Phonophobia and/or photophobia Yes No Decreased appetite Yes No Limited normal activity Yes No Placebo Group P value 24 23 7 (29.2%) 11 (45.8%) 3 (12.5%) 9 (37.5%) 9 (37.5%) 3.67 (1.71) 5.50 (1.84) 5.5 [2–8] 24.13 (9.55) 26.0 [4–40] 13 (56.5%) 20 (87%) 6 (26.1%) 17 (73.9%) 13 (56.5%) 1.52 (1.20) 7.04 (2.69) 7 [3–12] 35.17 (17.71) 34 [5–72] 0.109 0.031 0.416 0.027 0.311 0.0001 0.026 48.0 (17.57) 49 [10–70] 24 (100%) 18.33 (16.45) 15.0 [0–48] 17 (70.8%) 2.33 (2.87) 0 [0–8] 11 (45.8%) 0.50 (1.06) 0 [0–3] 5 (20.8%) 4.42 (1.39) 4.5 [2–7] 194.25 (54.08) 202 [56–340] 70.96 (17.44) 72 [20–96] 23 (100%) 40.17 (15.59) 42 [0–60] 22 (95.7%) 5.56 (4.62) 6 [0–13] 15 (65.2%) 4.30 (4.98) 0 [0–13] 11 (47.8%) 6.35 (1.86) 7 [2.5–8.5] 329.96 (99.26) 315 [110–475] 0.0001 5 (20.8%) 19 (79.2%) 12 (52.2%) 11 (47.8%) 0.025 0 (0%) 24 (100%) 7 (30.4%) 16 (69.6%) 0.012 6 (25%) 18 (75%) 14 (60.9%) 9 (39.1%) 0.028 1 (4.2%) 23 (95.8%) 7 (30.4%) 16 (69.6%) 0.045 6 (25%) 18 (75%) 14 (60.9%) 9 (39.1%) 0.028 0.10 0.0001 0.006 0.01 0.0001 0.0001 Data are reported as mean (SD), median [minimum–maximum], or number (%) as appropriate. P < 0.05 was considered significant. turbance of the nerve ending and the contractile mechanism at multiple dysfunctional endplates, resulting in trigger points.27,28 Chu further illustrated that entrapment of the nerve root could be documented with electromyographic studies.29 Thus, occipital blockade may result in local muscle relaxation and liberation of the entrapped nerve. There was considerable interpatient variability in the nerve location. The use of nerve stimulator technique improved accuracy, but required the patient’s co-operation for optimal detection of the nerve. Therefore, effective might not always be initially achieved, making repeated blocks necessary to increase the likelihood of success. A major limitation of this study is the short duration of follow-up. However, as our research activity is compliant with the principles enunciated in the Declaration of Helsinki,30 acting only in the patients’ interest and their well-being, we decided to limit the duration of this controlled clinical trial for a period of two weeks in order not to deprive the patients in the control group from any beneficence. Consequently, long-term outcome was not evaluated in this study. Another limitation of this clinical trial was the difficulty in blinding when numbness resulted in patients who received anesthetic blockade. In conclusion, the nerve stimulator-guided occipital nerve blockade is a treatment that provides relief of Occipital Nerve Blockade for Cervicogenic Headache • 95 CGH and accompanying symptoms for up to two weeks. This simple technique merits further investigation for patients suffering from CGH. 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