Potency and Stability of Intradermal Capsaicin: Implications for Use as a Human Model of Pain in Multicenter Clinical Trials.

Pavan Balabathula

doi:10.4172/2161-1459.1000142

Abstract

Intradermally injected capsaicin has been used extensively both as a human pain model and to assess analgesic efficacy. Factors such as dose, formulation, route, and site are known to affect its sensitivity. We determined whether potency and stability of capsaicin solutions were further sources of variability when following strict manufacturing guidelines. Capsaicin solution (1.0 mg/mL) was prepared according to Current Good Manufacturing Practice (cGMP) guidelines and aseptically filled into sterile amber borosilicate vials and stored at 5°C, 25°C, and 30°C. All samples were analyzed at one, three, six, and twelve months. Chemical stability was determined using HPLC and physical stability was evaluated by visual inspection of color changes, clarity, particulate matter, and product/ container closure abnormalities during each sampling time. Capsaicin intradermal injection was found to be sterile and retained 95% of the initial concentration for at least one year, regardless of studied storage temperatures (P<0.0001). Visual inspection indicated no changes in color, clarity, particulate matter, and product/ container closure abnormalities in all samples. These data show that capsaicin solutions (1.0 mg/mL) maintain their potency and stability over one year when manufactured according to cGMP guidelines. These results suggest that in clinical trials manufacturing of capsaicin solutions is recommended over extemporaneous compounding.

Highlights

Inflammatory substances, such as capsaicin, have been used experimentally to measure clinical pain dimensions of hyperalgesia and allodynia, characteristics of central sensitization [1,2,3,4,5]
Capsaicin-induced cutaneous sensitivity has been observed in a number of painful conditions, including post herpetic neuralgia [8], complex regional pain syndrome [9], fibromyalgia [10,11], rheumatoid arthritis [12], vulvodynia [13], unilateral sciatica [14], and multiple chemical sensitivity [15]
Attempts have been made to improve the sensitivity of the capsaicin model of allodynia and hyperalgesia by reducing sources of variability

Summary

Introduction

Inflammatory substances, such as capsaicin, have been used experimentally to measure clinical pain dimensions of hyperalgesia and allodynia, characteristics of central sensitization [1,2,3,4,5]. Capsaicin-induced cutaneous sensitivity has been observed in a number of painful conditions, including post herpetic neuralgia [8], complex regional pain syndrome [9], fibromyalgia [10,11], rheumatoid arthritis [12], vulvodynia [13], unilateral sciatica [14], and multiple chemical sensitivity [15]. These disorders may represent a common dysfunction in central processing of pain stimuli [16]. Capsaicin may represent an important aid in the study of pain mechanisms and to demonstrate the analgesic potential of new compounds

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