Instant Analgesic Effect of Sublingual Progesterone Dilution in Fibromyalgia

Original Article

Austin J Womens Health. 2019; 6(1): 1032.

Instant Analgesic Effect of Sublingual Progesterone Dilution in Fibromyalgia

Shilpa S¹* and Roby R²

¹Postdoctoral Studies, University of Mumbai, India

²Ex-Roby Institute, USA

*Corresponding author: Shilpa Shah, Postdoctoral Studies, University of Mumbai, Mumbai, India; E-mail: [email protected]

Received: January 10, 2019; Accepted: February 25, 2019; Published: March 04, 2019

Abstract

Fibromyalgia is a disorder chiefly characterized by widespread musculoskeletal pain. It is more common in women than men. Its severity is linked to the menstrual cycle with worsening of symptoms prior to menses. Varied medications like pain relievers, antidepressants and anticonvulsants are in use to relieve this condition, but there is no recognized cure. With this background, findings of the present pilot study could provide new approach for pain relief for fibromyalgia sufferers and perhaps also for other pain disorders. Functional MRI-brain (fMRI-brain) was done to examine brain activity for pain relief in response to a single dose of 0.5mg sublingual progesterone dilution in a woman suffering from fibromyalgia. Her pain symptoms were of headache, severe eye pain, back pain, muscle and joint pain. On sublingual administration of 0.5mg progesterone dilution the patient reported complete pain relief and the fMRI-brain showed an area of prominent activation in the posterior cingulated gyrus. Progesterone being a neurosteroid can possibly act through ion channelassociated membrane receptors to elicit rapid changes in signaling that can occur within seconds resulting in instant resolution of physical pain.

Keywords: Progesterone; Analgesic; Pain; Fibromyalgia; Sublingual; fMRIbrain

Introduction

Fibromyalgia is estimated to affect 2-8% of the population [1]. Its pathology connects to dysfunction of muscles and connective tissue as well as functional abnormalities in the central nervous system. There is extensive research evidence to support the view that the central symptom of fibromyalgia, namely pain, result from processes in the central nervous system and the condition is referred to as a “central sensitization syndrome” [1-5]. The chronic pain of fibromyalgia is pervasive and persistent. As neither the etiology nor mechanism of fibromyalgia is currently well understood, it is a tough challenge for patients as well as physicians to manage the fibromyalgia related chronic pain till now [6,7].

Fibromyalgia affects women twice as often as men [1]. It is common among patients with premenstrual syndrome and shares similarities and features with premenstrual dysphoric syndrome [8,9]. Menstrual cycle related hormonal fluctuations could be affecting the expression and severity of symptoms of fibromyalgia. A recent study published in the Journal of pain [10] has reported that lower levels of testosterone and progesterone are significantly associated with increased pain in Fibromyalgia. Progesterone levels naturally fluctuate in relation to the menstrual cycle; rising during ovulation and falling again before menstruation. It is a neurosteroid that can be metabolized within all parts of the central nervous system [11]. It is a neuromodulator, with neuroprotective and neurogenic properties that can regulate neurotransmission and myelination [12]. The present study discovers instant analgesic effect of low dose sublingual progesterone dilution.

Methods

Study subject

The subject was a 54 years old female patient (date of birth 12 November 1953) suffering from widespread body aches since puberty at the age of 13. At the age of 30 her complaints were diagnosed as fibromyalgia with severe headache, eye pain, back pain, muscle and joint pain. The pain had often been extreme and would worsen premenstrually. Her pain could only poorly be managed with Narcotics. Her right eye pain was so worse that she was suggested enucleation. Her sleep was affected and so did her day to day life. In 2006 she got started on the sublingual progesterone dilution therapy.

Personalized sublingual progesterone dose determination

Progesterone 50 mg/ml USP (Schein Laboratories, Florham, N.J.) suspended in sesame oil was used. It was diluted with normal saline to produce the progesterone dilutions 0.05 μg, 0.5 μg, 5 μg, 0.05 mg, 0.5 mg. To achieve an even suspension, the dilutions were vigorously shaken at each stage of the preparation and before use. 0.1 ml of these dilutions was administered sublingually to the patient beginning from 0.05 μg stepping up to 0.5 mg. Following administration of the sublingual progesterone dilution under the patient’s tongue, the patient was instructed to hold the medicine for 5 seconds before swallowing. After an additional 15 seconds, the patient was asked to rate her pain symptoms on the scale of zero to ten with ten being the most severe pain and zero indicating no pain at all [13].

Subject preparation

She was requested not to use her sublingual progesterone dilution dose for 72 hours prior to the scanning session.

fMRI-brain protocol

The fMRI investigation was done as an outpatient procedure. On arrival the patient was screened for safety in the magnetic environment. After getting positioned under the scanner, she was asked to rate her pain score on the scale of zero to ten (with ten being the most severe pain and zero indicating no pain at all). Her pain score was noted. Under the scanner when she was head stable a capsule containing 0.5 mg progesterone dilution was placed on her pursed lips. It is now that the imaging was started. Initial baseline BOLD imaging was performed and while continuing with the imaging: the patient was instructed to take in the capsule, crush and hold it sublingually for 5 seconds, and subsequently at 15 seconds she was asked to rate the pain score again. This single event continuous imaging ended in about 5 minutes post 0.5 mg sublingual progesterone dilution. The fMRI system was Magnetom Trio 3.0 Tesla (Siemens). Pulse sequence type was Echo-Planar imaging with parallel imaging parameter Generalized Autocalibrating Partial. Acquisition orientations were Axial, Sagittal, Coronal and Three-Dimensional.

Results

Based on the patient’s feedback during the personalized progesterone dilution dose determination; sublingual dose of 0.5 mg progesterone dilution was found to be most effective in alleviating her pain symptoms. When the fMRI-brain protocol was planned, by now the patient was on 0.5 mg sublingual progesterone dilution every 12 hourly for two years (2006-2008). Over this period, she had relief from pain: her sleep had improved and was able to do her daily activities without any limitations. The eye pain relief was so absolute that the suggested enucleation of the right eye was not required. Post withdrawal of sublingual progesterone 0.5mg for 72 hours (prior to the start of fMRI-brain imaging) she reported average pain symptom score of 8 on the scale of 0 to 10 (with ten being the most severe pain and zero indicating no pain at all). During the fMRI-brain imaging, after administration of her regular dose of sublingual progesterone dilution 0.5 mg, in 15 seconds she reported 0 pain symptom score (on the scale of 0 t0 10 with ten being the most severe pain and zero indicating no pain at all).

The fMRI-brain outcome highlighting significant change in the brain region post sublingual progesterone dilution 0,5 mg and forthwith pain relief are illustrated in the underneath figures (Figure 1, Figure 2, Figure 3 and Figure 4). It will be supportive to know the chief finding prior to taking into consideration details of each of these figures. Chiefly, although scattered noise was identified the bold imaging following sublingual administration of progesterone dilution 0.5 mg showed more prominent activation in a single area measuring about 12 mm in the posterior cingulated gyrus nearly along the posterior margin of Brodmann’s area 31 and 24. Figure 1: Images 1, 2, 3, 4 are the initial baseline BOLD images. It was 2.26 seconds later the sublingual administration of progesterone dilution 0.5 mg that the posterior cingulated gyrus showed prominent activation which lasted for 6.21 seconds (Figure 1: Image 6 and Figure 4: Images 1 & 2). Figure 2: Image 2 shows administration of 0.5 mg sublingual progesterone dilution and simultaneous activation in the posterior cingulated gyrus. It was also endorsed in the three-dimensional view of the f-MRI brain images (Figure 3).