Association of Hormonal Contraceptive Use with Headache and Temporomandibular Pain: The OPPERA Study.

AIMS: To determine the relationship between hormonal contraceptive (HC) use and painful symptoms, particularly those associated with headache and painful temporomandibular disorders (TMD). METHODS: Data from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study were used. During the 2.5-year median follow-up period, quarterly health update (QHU) questionnaires were completed by 1,475 women aged 18 to 44 years who did not have TMD, menopause, hysterectomy, or hormone replacement therapy use at baseline. QHU questionnaires evaluated HC use, symptoms of headache and TMD, and pain of ≥ 1 day duration in 12 body regions. Participants who developed TMD symptoms were examined to classify clinical TMD. Headache symptoms were classified based on the International Classification of Headache Disorders 3 (ICHD-3). Associations between HC use and pain symptoms were analyzed using generalized estimating equations and Cox models. RESULTS: HC use, endorsed in 33.7% of QHU questionnaires, was significantly associated with concurrent symptoms of TMD (odds ratio [OR]: 1.20, 95% CI: 1.06 to 1.35) and headache (OR: 1.26, 95% CI: 1.11 to 1.43). HC use was also significantly associated with concurrent pain of ≥ 1 day duration in the head (OR: 1.38, 95% CI: 1.16 to 1.63), face (OR: 1.44, 95% CI: 1.13 to 1.83), and legs (OR: 1.22, 95% CI: 1.01 to 1.47), but not elsewhere. Initiation of HC use was associated with increased odds of subsequent TMD symptoms (OR: 1.37, 95% CI: 1.13 to 1.66) and pain of ≥ 1 day in the head (OR: 1.37, 95% CI: 1.01 to 1.85). Discontinuing HC use was associated with lower odds of subsequent headache (OR: 0.82, 95% CI: 0.67 to 0.99). HC use was not significantly associated with subsequent onset of examiner-classified TMD. CONCLUSION: These findings imply that HC influences craniofacial pain, and that this pain diminishes after cessation of HC use.

A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.

Alterations in cellular energy metabolism have been implicated in chronic pain, suggesting a role for mitochondrial DNA. Previous studies reported associations of a limited number of mitochondrial DNA polymorphisms with specific pain conditions. In this study, we examined the full mitochondrial genomes of people with a variety of chronic pain conditions. A discovery cohort consisting of 609 participants either with or without a complex persistent pain conditions (CPPCs) was examined. Mitochondrial DNA was subjected to deep sequencing for identification of rare mutations, common variants, haplogroups, and heteroplasmy associated with 5 CPPCs: episodic migraine, irritable bowel syndrome, fibromyalgia, vulvar vestibulitis, or temporomandibular disorders. The strongest association found was the presence of the C allele at the single nucleotide polymorphism m.2352T>C (rs28358579) that significantly increased the risk for fibromyalgia (odds ratio [OR] = 4.6, P = 4.3 × 10). This relationship was even stronger in women (OR = 5.1, P = 2.8 × 10), and m.2352T>C was associated with all other CPPCs in a consistent risk-increasing fashion. This finding was replicated in another cohort (OR = 4.3, P = 2.6 × 10) of the Orofacial Pain: Prospective Evaluation and Risk Assessment study consisting of 1754 female participants. To gain insight into the cellular consequences of the associated genetic variability, we conducted an assay testing metabolic reprogramming in human cell lines with defined genotypes. The minor allele C was associated with decreased mitochondrial membrane potential under conditions where oxidative phosphorylation is required, indicating a role of oxidative phosphorylation in pathophysiology of chronic pain. Our results suggest that cellular energy metabolism, modulated by m.2352T>C, contributes to fibromyalgia and possibly other chronic pain conditions.

Dorsal clitoral nerve injury following transobturator midurethral sling.

INTRODUCTION: Transobturator slings can be successfully used to treat stress urinary incontinence and improve quality of life through a minimally invasive vaginal approach. Persistent postoperative pain can occur and pose diagnostic and therapeutic dilemmas. Following a sling procedure, a patient complained of pinching clitoral and perineal pain. Her symptoms of localized clitoral pinching and pain became generalized over the ensuing years, eventually encompassing the entire left vulvovaginal region. AIM: The aim of this study was to highlight the clinical utility of conventional pain management techniques used for the evaluation and management of patients with postoperative pain following pelvic surgery. METHODS: We described a prototypical patient with persistent pain in and around the clitoral region complicating the clinical course of an otherwise successful sling procedure. We specifically discussed the utility of bedside sensory assessment techniques and selective nerve blocks in the evaluation and management of this prototypical patient. RESULTS: Neurosensory assessments and a selective nerve block enabled us to trace the source of the patient's pain to nerve entrapment along the dorsal nerve of the clitoris. We then utilized a nerve stimulator-guided hydrodissection technique to release the scar contracture. CONCLUSION: This case demonstrates that the dorsal nerve of the clitoris is vulnerable to injury directly and/or indirectly. Assimilation of a time-honored pain management construct for the evaluation and management of patients' pain may improve outcomes while obviating the need for invasive surgery.

Genitofemoral and perineal neuralgia after transobturator midurethral sling.

BACKGROUND: Midurethral slings successfully treat stress urinary incontinence through a minimally invasive vaginal approach. Postoperative pain related to sling placement can occur and poses both diagnostic and treatment dilemmas. CASE: Four years after transobturator midurethral sling placement, the patient presented with complaints of left labial pain and dyspareunia since surgery. Using sensory mapping and a nerve stimulator, the problem was identified in the distribution of the genitofemoral nerve. Conservative therapy with a centrally acting neuromodulatory drug and nerve block relieved the pain. CONCLUSION: Postsling neuralgia diagnosis using sensory mapping and a nerve stimulator aids in indentifying the nerve involved and in successful conservative treatment with a nerve block.

Altered central sensitization in subgroups of women with vulvodynia.

OBJECTIVE: To investigate the clinical correlates of central nervous system alterations among women with vulvodynia. Altered central sensitization has been linked to dysfunction in central nervous system-inhibitory pathways (e.g., γ-aminobutyric acidergic), and metrics of sensory adaptation, a centrally mediated process that is sensitive to this dysfunction, could potentially be used to identify women at risk of treatment failure using conventional approaches. METHODS: Twelve women with vulvodynia and 20 age-matched controls participated in this study, which was conducted by sensory testing of the right hand's index and middle fingers. The following sensory precepts were assessed: (1) vibrotactile detection threshold; (2) amplitude discrimination capacity (defined as the ability to detect differences in intensity of simultaneously delivered stimuli to 2 fingers); and (3) a metric of adaptation (determined by the impact that applying conditioning stimuli have on amplitude discriminative capacity). RESULTS: Participants did not differ on key demographic variables, vibrotactile detection threshold, and amplitude discrimination capacity. However, we found significant differences from controls in adaptation metrics in 1 subgroup of vulvodynia patients. Compared with healthy controls and women with a shorter history of pain [n=5; duration (y) = 3.4 ± 1.3], those with a longer history [n=7; duration (y) = 9.3 ± 1.4)] were found to be less likely to have adaptation metrics similar to control values. DISCUSSION: Chronic pain is thought to lead to altered central sensitization, and adaptation is a centrally mediated process that is sensitive to this condition. This report suggests that similar alterations exist in a subgroup of vulvodynia patients.

Evaluation and treatment of dyspareunia.

Dyspareunia affects 8-22% of women at some point during their lives, making it one of the most common pain problems in gynecologic practice. A mixture of anatomic, endocrine, pathologic, and emotional factors combine to challenge the diagnostic, therapeutic, and empathetic skills of the physician. New understandings of pain in general require new interpretations concerning the origins of pain during intercourse, but also provide new avenues of treatment. The outcomes of medical and surgical treatments for common gynecologic problems should routinely go beyond measures of coital possibility, to include assessment of coital comfort, pleasure, and facilitation of intimacy. This review will discuss aspects of dyspareunia, including anatomy and neurophysiology, sexual physiology, functional changes, pain in response to disease states, and pain after gynecologic surgical procedures.

Overlap between orofacial pain and vulvar vestibulitis syndrome.

OBJECTIVES: To explore the prevalence of orofacial pain (OFP) among patients with vulvar vestibulitis syndrome (VVS) and to examine the relationship between signs and symptoms of OFP and clinical characteristics of women with VVS, we investigated differences in psychologic characteristics and severity of painful intercourse. METHODS: In this cross-sectional exploratory study, 137 women with VVS completed questionnaires that assessed levels of pain, anxiety, somatization, and presence of signs and symptoms suggestive of clinical and subclinical OFP. Demographic data were gathered from medical records. RESULTS: OFP was found to be a highly prevalent (78%) condition among women with VVS. Compared with women who had no OFP symptoms (n=30), those with symptoms (n=64) reported higher levels of anxiety (45.0 vs. 37.8, Bonferroni adjusted P=0.017), somatization (125.2 vs. 96.0, Bonferroni adjusted P<0.001), and psychologic distress (62.8 vs. 56.0, Bonferroni adjusted P=0.002). Although we observed a similar trend among women with subclinical OFP (n=43), this trend only reached statistical significance with respect to somatization. Differences were not detected for demographics, duration of pain, and severity of pain during intercourse across the 3 groups. DISCUSSION: OFP is a common condition among women with VVS. Because severity and duration of painful intercourse did not differ by OFP classification but psychologic characteristics did, we must begin to question a unidimensional focus on vestibular mucosa as a reason for pain and persistent distress.

Overnight 5% lidocaine ointment for treatment of vulvar vestibulitis.

OBJECTIVE: To assess the effectiveness of nightly application of 5% lidocaine ointment for treatment of vulvar vestibulitis. METHODS: Over 17 months, we assessed women presenting to our pain clinic for evaluation of introital pain; 61 women met the criteria for vulvar vestibulitis and participated in a treatment trial. We measured daily pain and intercourse-related pain using a 100-mm visual analog scale. We compared ability to have intercourse and pain ratings before and after treatment, and investigated whether prior treatment or gynecologic comorbidities predicted response to treatment. RESULTS: After a mean of 7 weeks of nightly treatment, 76% of women reported ability to have intercourse, compared with 36% before treatment (P =.002). Intercourse-related pain score was 39.11 (95% confidence interval [CI] 30.39, 47.83) points lower after treatment (P <.001), with a decrease of 10.37 (95% CI 3.53, 17.21) points in daily pain score (P =.004). We found no association between response to prior episodic use of lidocaine and response to nightly therapy with lidocaine ointment. Few patient characteristics predicted response to treatment; however, women with interstitial cystitis and other vulvar conditions were least likely to benefit. CONCLUSION: Long-term, nightly application of 5% lidocaine ointment shows promise as a treatment for management of vulvar vestibulitis; a randomized, double-blind, clinical trial is warranted.