Baclofen

In patients suffering from vulvodynia, an exaggerated response to inflammation due to a decreased ability to downregulate the inflammatory activity is currently seen as a cornerstone in disease pathogenesis.³ Vulvodynia has been recognized as a cytokine-mediated pain syndrome, characterized by increases in proinflammatory cytokines i.e IL-8, and decreases in anti-inflammatory cytokines i.e. IL-10.⁴ Localized neuroinflammation may alter ion channel activity of peripheral axons, resulting in. sensitization and enhanced perception of pain in the local area.⁵

Within the context of neuroinflammation, it would be very likely that the synthesis of the autocoid bioactive lipids from the classes N-acylethanolamides (among which palmitoylethanolamide) is disturbed

Baclofen is a derivative of the neurotransmitter γ-aminobutyric acid (GABA). It is believed to work by activating (or agonizing) GABA receptors, specifically the GABAB receptors.² Its beneficial effects in spasticity result from its actions in the brain and spinal cord.¹

Topical and systemic replenishment of PMAE may bring relief from pain by targeting tissue components of the vaginal epithelium, such as free nerve endings of nociceptors, immunocompetent cells, and epithelial cells.

Baclofen has been studied for the use in women experiencing:

• Vulvodynia^4,6
• Proctodynia^4,6
• Vestibulodynia⁷

PMAE has been studied for use in women experiencing:

• Vulvodynia^6,7

Vulvar and Anal Pain

A 33-year-old woman with intractable chronic vulvar and anal pain had to abstain from sexual intercourse and could neither cycle nor sit for more than 5 min. The patient did not respond to standard treatments. We prescribed a combination of topical baclofen 5 % and palmitoylethanolamide 400 mg, three times daily. After 3 months her symptoms decreased more than 50 % and sexual intercourse was possible again without pain.⁶

Vestibulodynia

In a retrospective evaluation of 38 patients with provoked vestibulodynia (PV), 2% amitriptyline and 2% baclofen cream was used. After 33 weeks of treatment, 53% of women reported much (>60%) improvement, 18%, reported moderate (30-60%) improvement , and 29% reported no or little (<30%) improvement. On self-administered questionnaires, patients reported a decrease in the extent to which the condition interfered with social activities (p=0.17), easier lubrication (p=0.22), and lower pain with intercourse (p=0.05). No patients experienced systemic side effects.⁷

Baclofen Cream has been studied at doses of 2-5% applied to the vulvar, vestibular and anal areas up to three times daily^4,7

PMAE has been studied at doses of 400mg orally three times daily.⁶ PMAE is available as 600mg tablets and may be taken twice daily for the same equivalent daily dose.

Although Nyirjesy⁷ reported no systemic side effects with topical baclofen therapy, the most common effect when taken orally is transient drowsiness (10 to 63%). In one controlled study of 175 patients, transient drowsiness was observed in 63% of those receiving baclofen compared to 36% of those in the placebo group. Other common adverse reactions are dizziness (5 to 15%), weakness (5 to 15%) and fatigue (2 to 4%).

Neuropsychiatric: Confusion (1 to 11%), headache (4 to 8%), insomnia (2 to 7%); and, rarely, euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizure.

Cardiovascular: Hypotension (0 to 9%). Rare instances of dyspnea, palpitation, chest pain, syncope.

Gastrointestinal: Nausea (4 to 12%), constipation (2 to 6%); and rarely, dry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhea, and positive test for occult blood in stool.

Genitourinary: Urinary frequency (2 to 6%); and rarely, enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, hematuria.

Other: Instances of rash, pruritus, ankle edema, excessive perspiration, weight gain, nasal congestion. Some of the CNS and genitourinary symptoms may be related to the underlying disease rather than to drug therapy. The following laboratory tests have been found to be abnormal in a few patients receiving baclofen: increased SGOT, elevated alkaline phosphatase, and elevation of blood sugar.