OUTLINE

CASE LBP caused by OA

PAIN PATHWAY PAIN SENSITIZATION PAIN MANAGEMENT

Role of Pain Medications in the Pain Pathway

Prevention of Pain Sensitization Pain Management Guidelines

CASE

56 year old, Female, Public School Teacher

DM type 2, well controlled Obese Type 2 Complaints : Hip and knee pain Other complaints: “ngalay of her

lower extremeties”

QUESTION #1

What is the cause of the patient’s pain?

Based on his history what type of pain is he experiencing? Nociceptive Neuropathic Mixed Acute Chronic

Pain, the predominant symptom in OA, is multidimensional in its nature and mediated through a variety of factors.

Osteoarthritis (OA) chronic pain, involve nociceptive as well as nonnociceptive components, including neuropathic components, due to peripheral inflammation and central sensitization C. S. Bonnet and D. A. Walsh

Osteoarthritis

Mart van de Laar, Joseph V. Pergolizzi Jr, Hans-Ulrich Mellinghoff The Open Rheumatology Journal, 2012, 6, 320-330 1874-3129/

Low Back Pain

Many patients with chronic lower back pain have no radiculopathic or anatomic abnormalities that could explain their symptoms.

Evidence suggests that sensitization of the central nervous system (CNS) may perpetuate the perception of pain in the absence of ongoing tissue damage.

Borenstein DG. Epidemiology, etiology, diagnostic evaluation, and treatment of lowback pain. Curt Opin Rheumatol. 2001;13:128-134.

How is PAIN produced?

PAIN PATHWAY

Bingham B et al. (2008) The molecular basis of pain and its clinical implications in rheumatology

PAIN PATHWAYTRANSDUCTION

Journal of Medicinal Chemistry, 2007, Vol. 50, No. 11

PAIN PATHWAY SYNAPTIC TRANSMISSION 

Journal of Medicinal Chemistry, 2007, Vol. 50, No. 11

PAIN PATHWAY

Ascending and Descending Modulation

Perception

Journal of Medicinal Chemistry, 2007, Vol. 50, No. 11

QUESTION #2

What will be your goal in managing this patient’s pain? Decrease Pain score by -2 from baseline Increase ability to perform ROM

exercises Prevent chronicity/sensitization of pain

Osteoarthritis

The pain experience in OA results from interactions between inflammation and other features of the disease including: radiological severity, innervation of articular structures, central and peripheral sensitization

and psychological factors

CENTRAL SENSITIZATION

The Journal of Pain, Vol 10, No 9 (September), 2009: pp 895-926

PAIN SENSITIZATION: ACUTE TO CHRONIC PAIN

American Family Physician, Gottschalk et.al MAY 15, 2001 / VOLUME 63, NUMBER 10

PREVENTION OF PAIN SENSITIZATION

MULTIMODAL EFFICACY OF PAIN MEDICATIONS

Ultimately, multimodal approaches that address multiple sites along the pain pathway may prove necessary to adequately prevent central sensitization in many surgical procedures.

American Family Physician, Gottschalk et.al MAY 15, 2001 / VOLUME 63, NUMBER 10

Working Group A.M.A.D.E.U.S. Basic Course in Treatment of Chronic Pain, Cologne 2003.

MANAGEMENT GOALS: Prevent Chronification of pain: breaking the

vicious circle

QUESTION #3

What will be the factors that you will consider in choosing the right pharmacologic intervention? (based on your priority) Efficacy of the drug- alleviate the

amount of pain the fastest Side-effect profile of the drug Mode of Action- targets majority of the

processes in the pain pathway Pain Management Guidelines

Osteoarthritis

Although pain is the most pressing problem facing people with OA, adequate pain relief is frequently not achieved maybe because: (a) lack of professional medical attention, (b) failure to incorporate

nonpharmacological measures such as weight loss and exercise into the treatment plan, and

(c) overreliance on monotherapy.

Arthritis Foundation, Association of State and Territorial Health Officials, Centers for Disease Control and Prevention. National arthritis action plan. A public health strategy. Internet: CDC; 1999 [cited September 26, 2003]

PAIN MANAGEMENT CONSIDERATIONS

Selective and nonselective

NSAIDs

Tramadol/paracetamol combination

Mild Pain X

Moderate Pain X X

Severe Pain X

Acute Vs Chronic Pain X X

Neuropathic Pain X

Anti-inflammatory effect

X

Pediatric Use X

Geriatric Use X

Patients with renal failure

can still be used to patients with moderate renal impairment

Patients with CV Risks X Pergolizzi Jr et al Journal of Pain Research 2012:5 327–346

Role of Pain Medications in the Pain Pathway

PAIN INTERVENTION

American Family Physician, Gottschalk et.al MAY 15, 2001 / VOLUME 63, NUMBER 10

PAIN MEDICATION TRANSDUCTION TRANSMISSION DESCENDING MODULATION

NSAIDs xLocal Anesthetics xAnti-epileptic drugs x

Opioids x xPeripheral and Spinal Nerve Blocks x

Epidural and intrathecal analgesics

x

Antidepressants XSNRIs x

Role of Pain Medications in the Pain Pathway

January 2009 Vol 5 No 1 Bingham et.al.

PAIN MANAGEMENT GUIDELINES

IASP Recommendations for the Pharmacological Management of Neuropathic Pain

The role of fixed-dose combinations in chronic pain management

TRAMADOL/PARACETAMOL

Potential advantages of a fixed-dose tramadol/paracetamol analgesic product: include a broader analgesic spectrum a complementary pharmacokinetic

profile potentially synergistic analgesic effect greater convenience (possibly resulting

in better compliance, thus, improved therapy)

an improved ratio of efficacy to adverse effects.

Pergolizzi Jr et al Journal of Pain Research 2012:5 327–346

TRAMADOL peak = 2-3 hrs T1/2 = 6 hrs

TIME

Dru

g Eff

ect

APAP peak = 30 min T1/2 = 2 hrs

Tramadol/Paracetamol: Rationale

In combination, T1/2 extends to 7-9 hours

Result of combination:– Fast onset of action– Prolonged action

Pergolizzi Jr et al Journal of Pain Research 2012:5 327–346

CLINICAL EVIDENCE OF USING TRAMADOL/PARACETAMOL

OsteoarthritisLow Back Pain

Ann Rheum Dis 2010;69(Suppl3):273

BACKGROUND

NSAIDs are commonly prescribed for knee OA pain. However, flare ups of OA pain or poor control with NSAIDs alone are common and necessitate the addition of other analgesics with different mechanisms, such as tramadol

OBJECTIVES

The purpose of this study is to compare the efficacy of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/APAP) with that of nonsteroidal anti-inflammatory drugs (NSAIDs) as maintenance therapy following tramadol/APAP and NSAID combination therapy in knee osteoarthritis (OA) pain which was inadequately controlled by NSAIDs.

DESIGN: This was a randomized, multicenter, open comparative study in out-patients at six sites.

Why do you think it is a better choice to use Tramadol/APAP FDC as a maintenance drug for OA pain compared to NSAIDs?

Our speculation is that in our subjects with inadequately controlled knee OA pain, chronic continuous pain stimuli from diseased joints might have caused sustained activation of sensory fibers supplying the dorsal horn in the spinal cord and change in the nature of the pain and resulted in central sensitization and making pain refractory to NSAIDs.

Tramadol is reported to have a dual mechanism of action which are good for the control of central sensitization; μ-opioid receptor binding and inhibiting reuptake of serotonin and

norepinephrine. It is therefore probable that

tramadol/APAP add-on therapy eased central sensitization and made it easier to control knee OA pain.

CONCLUSION

In conclusion, when added to NSAID, tramadol/APAP was generally well tolerated and significantly improved knee OA pain which was previously refractory to NSAID therapy.

In those subjects who showed favorable response to tramadol/APAP and NSAID combination therapy, both tramadol/APAP and NSAIDs were effective at maintaining the pain-reduced state and there was no significant difference in efficacy between tramadol/APAP and NSAIDs.

PAIN MANAGEMENT GUIDELINES

Conclusion

Considering the Long-term treatment with NSAIDs can cause various side effects, Tramadol/Paracetamol can therefore be considered as the good candidate for maintaining pain improved state of Osteoarthritis patients

- http://www.who.int/cancer/palliative/painladder/en/