Low Back Pain: Treatment and New Evidence Clinical Trial Dolor

Professor Marco Antonio Naslausky Mibielli Serra dos rgos University-Teresopolis Head of Service from Clinical Hospital University Master in Medicine - Orthopaedic and Traumatology

Low Back Pain

Low Back Pain (LBP) = Symptom of musculoskeletal disorders involving the lumbar vertebrae

Progression of LBP:
Acute - subchronic - chronic - recurrent (severe acute episodes)

Mechanical Causes Triggers Contributing conditions

TYPES OF PAIN
Nociceptive Pain: caused by activity in neural pathways in response to potentially tissuedamaging stimuli. Mixed Type: caused by a combination of both primary injury or secondary effects. Neuropathic Pain: iniciated or caused by primary lesion or dysfunction in the nervous system.

Neuropathic Pain component in Low Back Pain

Presence of a lesion or disruption to primary sensory neurons (peripheral, dorsal) due to:
Trauma Compression Tumor Ischemia Inflammation: metabolic disturbances, degenerative disorders or cytotoxic substances

Nervous system dysfunction Hyperalgesia and allodynia due to cytokine release (NGF, TNF, NFkappaB)

Patients with Low Back Pain: Targets of Drug Therapy

Rapid and efficient amelioration of pain Restoration of mobility Improvement of sleep Improvement of reduced daily activities Fitness for work Avoidance of chronification

Diclofenac - Mechanisms of Actions:

Anti-inflammatory - Analgesic - Antipyretic Inhibition of Prostaglandin Synthesis by Inhibition of Cyclooxygenases (COX) - Moderate Preference to block COX-2 ! Inhibition of Lipoxygenase Pathways - Reducing Formation of Leukotriens Inhibition of Phospholipase A2 Blockade of Voltage-dependent Sodium Channels Blockade of Acid-sensing Ion Channels Modulation of Potassium Channels (ASICs)

Characteristics of B-Vitamins B1 and B6

B-Vitamins counterract nerve damage by various mechanisms Vitamin B1 formation of Acetylcholine transmission of impulses from nerves to muscles regeneration of the nervous system after strain reduction of hyperexcitability lessening of Na currents alterations in injured neurons suppressing thermal hyperalgesia Vitamin B6 modulates GABA release from pre-synaptic cells influences biosynthesis of neurotransmitters serotonin, epinephrine, GABA Vitamins B1 and B6 activate cGMP involved in the inhibition of thermal hyperalgesia

DOLOR - Primary Study Objective

Percentage of patients with pain reduction: VAS < 20 mm Patients satisfaction after 3 days of treatment allowing them to terminate the study Comparison of treatment groups: DB: Fixed combination of diclofenac + vitamins B1, B6, B12 versus D: Diclofenac monotherapy

DOLOR: Secondary Study Endpoints

Number of patients with pain reduction: VAS < 20mm Patients satisfaction after 5 and 7 days of treatment allowing them to terminate the study
Severity of pain (VAS) Finger-floor-distance (FFD) as parameter of motility Patients functionality questionaire (PFQ)

DOLOR - Primary study objective Results after 3 days of treatment - Visit 2

Study completed Due to clinical success Group DB n = 187 n % 87 46.5 Group D n = 185 n % 55 29.7

Due to insufficient efficacy

Due to side effects Study continued (n)

10

5.3

10

5.4

3 87

1.6

0 120

success rate: 16.8%; OR: 2.1 Chi2 = 12.06; p = 0.0005

Low Back Pain - Conclusions

The symptoms most patients are suffering appear to be related to functional pathology, psycho-social factors and environmental components Pain may be of nociceptive and neuropathic origin Drug treatment should be multi-modal Short term administration of Diclofenac is a potent choice for treatment of LBP relief Vitamins B1, B6, B12 provide various effects counteracting nerve damage and extent nociceptive pain treatment by Diclofenac with potent activity against neuropathic pain