Onabotulinum toxin for Pelvic pain

Philip Toozs-HobsonConsultant Urogynaecologist

Birmingham UK

Declaration

• I was sponsored by Allergan to travel to and attend this meeting

• I work as a consultant for Allergan and Astellas • I was an author on the RELAX study • I have been involved in Allergan and Astellas

sponsored trials• I undertake private practice

Onabotulinum Toxin

• Growing body of evidence

• Mainly case reports– Relatively rare

• Difficult to classify for research

What can you use Botox for…• Ophthalmic

– Strabismus– Blepherospasm

• MSK– Corticollis– Cervical dystonia

• Cosmetic

• Neurological – Migraines– severe primary axillary

hyperhidrosis

• Urological– NDO/UDO

Botox and pain

• Torticollis• Vulvodynia• Back pain• Fibromyalgia• Tennis elbow• Post mastectomy pain

• TMJ pain• Chronic prostatic pain• Whiplash• Tendonitis• Premature ejaculation• Anal fissures

Mechanism of action

Mechanism of action

Facts

• Botox takes min 48 hours to get flaccid paralysis

• Pain relief almost instantaneous

• Botox migrates up nerves

Muscle contraction Peripheral sensitisationCentral sensitisation

BOTOX®: An innovative treatment for OAB with a dual mechanism of action1–3

Blocks peripheral release of

neurotransmitter at presynaptic

cholinergic nerve terminals

Blocks release of neurotransmitters

and down regulates expression of

receptors associated with sensory afferent

pathway

BOTOX® Targets boththe efferentand afferent pathway

Treatment benefit:Detrusor muscle relaxation Treatment benefit:

Reduced urgency

BOTOX® targets both the afferent and efferent pathways

Acetylcholine Sensory neuropeptides and receptors

Sympathetic nervous system activity maintained as bladder

fills

Reduced parasympathetic nervous system activity in

response to bladder distension

Efferent pathway Afferent pathway

OAB, overactive bladder.

1. BOTOX® Summary of Product Characteristics, Allergan2. Purves D, et al. Autonomic Regulation of the Bladder. Neuroscience. 2nd edition. 2001.3. Apostolidis A, et al. Eur Urol 2006;49:644–50.

Site of action

• NMJ

• Autonomic ganglion

• Postganglionic parasympathetic nerve ending

• Postganglionic sympathetic nerve endings which use Ach

Nerve interactions

Nerve interactions

Differential diagnosis

• Vulvadynia• Atrophic vaginitis• PNE– After vaginal surgery

• Interstitial cystitis• Visceral hypersensitivity• Chronic Pelvic pain• Fibromyalgia

• MS• Vaginismus• Myofascial trigger

points• Sacro-iliac joint pain• Psoas problems• Faccet joint problems• Referred hip pain

Assessment

• History – Onset – Try to differentiate cause in history

• Examination– Pain mapping

• Treatment– Relaxation/PFE’s

Technique

• Pain map with patient awake

• GA 100U split doses into trigger points – Using pudendal needle

• Can do in outpatients in the brave– Using blue or green needles

A prospective cohort study

• 12 women• dyspareunia (80 vs 28; P = 0.01)• non-significant reductions in non-menstrual

pelvic pain (64 vs 37)• Pelvic floor muscles manometry showed a

37% reduction in resting pressure• Jarvis et al ANZJOG 2004

Largest review >400 patients• four subgroups: BPS/IC (n = 157)• CPP (n = 98), vulvodynia• dyspareunia (n = 40)• “other” (n = 113).

• complaints of voiding dysfunction (70%), dyspareunia (54%)• mean PUF score of 15.9 ± 6.4• positive potassium sensitivity test in 83%. • Urodynamics revealed a maximal urethral pressure of 131 cm of water

and an abnormal uroflow in 80%. • benefit in all groups (50%, 67%, 73%, and 77% for vulvodynia, CPP, BPS/IC,

“other”). • International Urogynecology Journal • Volume 20, Number 9 (2009), 1047-1053,

Our results

• Have treated around 30 patients

• About a 70% response rate

• Lasts at least 6 months – Side effects: urinary incontinence, retention,

faecal incontinence

Refractoy Myofascial trigger points

Methods31 patients (2005-10) mainly 300 U•Mean age 55

•Median pain 9.5/10– 15 repeat injections (at

median of 4 months)

•17 OPD treatment

Results • 52% pain free• Median score 3/10

• Side effects – Urinary retention (3)– faecal incont (2)– Constipation/pain (3)

• But improved in 15!

Adelowo et al Female Pelvic Med Reconstructr surg 2013

Conclusions

• Increasing understanding of Mechanisms of action of Botox

• Increasing data on safety

• Can be very useful with careful patient selection