3. PAIN
• Greek goddess – ‘POINE’ Pain
• It is defined as ‘’ Unpleasant sensory &
emotional experience associated with actual
or potential damage or described in terms of
such damage” – IASP 1974
• In simple words, patient says ‘it hurts’
• Why are we discussing this topic ?
• What is the relevance to today’s session ?
4. Epidemiology
• World over 22% patients in chronic pain
• Economic impact unimaginable
• India – 35 Crores (1947), 117 Crores (2010)
• Survival rate 32-35 yrs (1947), 47yrs (1990),
67 yrs (2010)
• Diabetic population 25 % by 2020
• Age related degenerative disorders
• ‘Empty Nest Syndrome’
5.
6. TYPES OF PAIN
• SUPERFICIAL/CUTANEOUS PAIN
• DEEP NON-VISCERAL PAIN
• VISCERAL PAIN
• REFERRED PAIN
• NEUROPATHIC PAIN
• PSYCHOGENIC/FUNCTIONAL PAIN
7. TYPES OF PAIN
1. ACUTE PAIN
It is related in time & the severity is proportional
to the healing of an injury or disease. As healing
progresses pain decreases.
2. CHRONIC PAIN
The same pain will be termed as chronic and the
pain persists beyond the normal healing period
for that particular injury or disease. It could be
because of recurrent injury or by an unexplained
mechanism
8. Can Acute Pain Evolve Into Chronic
Pain? (The Theory)
• Extensive and Persistent cascade of
neurochemical mediators triggered by tissue
injury
• Stimulate A beta fibers which connect in the
Rexed lamina of the spinal cord to sprout,
grow and connect to A delta fibers
• This then may progress to long-term,
permanent, neurological change that can lead
to Sensitisation, Allodynia, Hyperalgesia
Canadian Consortium on Pain Mechanisms, Diagnosis and Management-2004
9. Sensitisation
10
Hyperalgesia
8 Normal
pain
response
Pain intensity
6 Injury
4
Allodynia
2
0
Stimulus intensity
Gottschalk A, et al. Am Fam Physician. 2001;1979-1984.
10. WHY CHRONIC PAIN SHOULD BE
TREATED ?
• Vocational, social, family dysfunction
• Extensive, costly, nonproductive inv. & tr.
• Mental & Physical suffering
• ↑ Disability costs, ↑health care costs
• ↓ Immune response
• Death often by suicides
• Distorted Analysis
11. WORLD IS TRAVELLING FROM
INVASIVE OPTIONS TO
NONINVASIVE WAYS OF
HANDLING THE SITUATION
12.
13. Receptors at Skin level
• Touch
• Temperature
• Tactile sensation
• Light pressure
• Deep pressure
• Free nerve endings
• Unknown receptors???
17. Recent Developments
• Move from empirical therapies to a
mechanism based approach
• Newer drugs targeting specific receptor
subtypes
• Evidence Based Medicine
• International Guidelines, Cochrane Review
• Multidisciplinary approach
Anita Holdcroft, Ian Power. Clinical Review – Recent Developments of management
of pain. In BMJ 2003; 326; 635.
18. “Real People & Real Pain”
What are the Emerging
Pharmacological &
Nonpharmacological Aspects in
Pain Management ?
19. Emerging Pharmacological Aspects
• Local applicants
• Role of paracetamol
• Role of NSAID’s ; Cox-2 Inhibitors
• Role of Opioids
• Option of Multimodal Analgesia
• Options for Neuropathic Pain
• Future prospects
20. SUPERFICIAL/CUTANEOUS PAIN
• Rubefacients (salicylates & nicotinamides )
offer lesser pain relief than NSAID’s topical
application – 2009
• Topical NSAID’s provide good pain relief with
lesser side effects than oral NSAID’s - 2010
• Capsaicin local application for neuropathic
pain may be of help if other therapies donot
work – May 2009
22. NSAID’s, Cox-2
• Does Cox-2 Inhibitors Still Have a Role ?
• Celecoxib (Celebrix) currently used (30 times
stronger inhibition of Cox-2 over Cox-1)
• Rofecoxib (Vioxx) & Valdeicoxib(Bextra) 2004;
Risk of Myocardial Infarction & CVA (300
times stronger inhibition of Cox-2)
Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C (June 2006).
"Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk o
. BMJ 332 (7553): 1302–8. doi:10.1136/bmj.332.7553.1302. PMID 16740558 (138 trials, 1,50,000 patients)
23. NSAID’s, Cox-2
• Cox 2 Inhibitors Use – Colo-rectal polyps,
Menstrual cramps, RA, Psoriatic arthritis,
Sports Injuries, Neuroblastomas, cancers
• Side effects – Insomnia, diarrhoea, pain
abdomen, nausea, ulcers, perforations (lesser
extent ?). Risk of MI, CVA
Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C (June 2006).
"Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk o
. BMJ 332 (7553): 1302–8. doi:10.1136/bmj.332.7553.1302. PMID 16740558 (138 trials, 1,50,000 patients)
24. Multimodal Analgesia
• Opportunities to intervene and diminish pain
exist in multiple points along the pain
pathway
• It is synergistic to use combination drugs to
target multiple points of pain pathway for
pain control
• In effect – reduced doses of each analgesic,
improved pain control with synergistic
approach, reduced side effects
Raffa RB. J Clin Pharm Ther 2001;26:257
25. Tramadol (Tapentadol) +
Paracetamol
• Tramadol – binds to μ receptors & also
inhibits uptake of serotonin& norepinephrine
• Tapentadol – μ receptors & norepinephrine
uptake inhibition
• Paracetamol – inhibits nitric oxide
• Both in effect inhibit release of substance P
and hence pain relief
Paul et al. Analgesic efficacy & safety of Tramadol/acetaminophen combination in treatment
of CLBP; a multicenter outpatient, randomised, double blind, placebo controlled trial. The
Journal of Rheumatology 2004; 31; 2454-63
26. DEEP NON-VISCERAL PAIN
• Paracetamol offers better Pain Relief than
Placebo in OA – 2009
• Early ambulation helpful in LBA, however
patients with sciatica have no or little benefit
from bed rest – 2010
• Muscle relaxants are helpful non-specific back
pain
• NSAID’s provide pain relief in acute & chronic
low back pain for short term - 2011
27. DEEP NON-VISCERAL PAIN
• Glucosamine (Rotta Brand) was superior to
Placebo - 2009
• Opioids in long-term chronic pain is still
debatable – 2010
• Local corticosteroid injection provides short
term relief in Carpal Tunnel Syndrome – 2009
• IA steroid offers rapid and short term relief in
OA knee when compared to IH which has
slower and sustained effect - 2009
28. NEUROPATHIC PAIN
• Antidepressants for neuropathic pain;
effective in 1 in 3 – 2010
• Systemic administration of Lidocaine
neuropathic pain better than placebo - 2009
• Gabapentin effective in chronic pain but
inconclusive in acute pain – 2010
• Pregabalin effective in Neuropathic Pain &
Fibromyalgia but not acute pain - 2010
29. NEUROPATHIC PAIN
• Tramadol is effective in neuropathic pain –
2009
• Lamotrigine seems to be ineffective in
neuropathic pain – 2011
• Topical Lidocaine for PHN – Not a first line
treatment – July 2008
30. Interventional Pain Management
It is the discipline of medicine devoted to the
diagnosis and treatment of pain related
disorders principally with the application of
interventional techniques in managing sub
acute, chronic, persistent and intractable pain,
independently or in conjunction with other
modalities of treatment
31. What are those techniques?
• Non imaging assisted interventions
• Fluoroscopy assisted interventions
• USG Assisted interventions
• CT guided interventions
• Advanced pain management therapies
• Invasive neurosurgical techniques
47. Benefits of IPM
Procedures
• Non-analgesic benefits – limitation of side
effects, improved QOL, weight gain
• Less sedated, alert and satisfied patients
• Combination of medications and interventions
• Meaningful expectation
• Imaging assistance offers safety & accuracy
48. Some other Issues
• Meralgia Paresthetica – RCT
Required
• Vitamin B – Variable
• Trigeminal Neuralgia –
Nonanticonvulsants
• Vertebroplasty – JAMA
• Disc problems – surgeries
• Injection therapies for back
49.
50. CONCLUSIONS
• Pain is the one of the most common reasons that
people seek medical attention, it needs to be
managed aggressively and systematically
• Treat acute pain promptly & aggressively to possibly
avoid chronic pain
• Synergy: use combination drugs to target multiple
points of pain pathway
• Multi-modal management of pain can provide better
efficacy with reduced side effects
Hinweis der Redaktion
9402 Final Show 2 Nov 21, 2012 DRAFT Arachidonic acid is a polyunsaturated fatty acid , one of the essential fatty acids required by most mammals. It is present in the membranes of the body's cells , and is a precursor in the production of eicosanoids : the prostaglandins , thromboxanes , prostacyclin and the leukotrienes . A prostaglandin is any member of a group of lipid compounds that are derived from fatty acids and have important functions in the animal body. They are mediators and have a variety of strong physiological effects; although they are technically hormones they are rarely classified as such. There are two pathways for metabolism of arachidonic acid to prostaglandins, mediated by COX-1 and COX-2. COX-1 is constitutive and is responsible for the production of prostaglandins that protect the GI tract and maintain normal platelet function. COX-2 controls the production of prostaglandins that mediate inflammation and pain. 1,2 NSAIDs inhibit both COX-1 and COX-2 and are non-specific in their mode of action, controlling pain and inflammation but also causing characteristic adverse effects. 3 New strategies have focused on the development of therapeutic agents with pharmacological activity based on specific inhibition of COX-2. 3 The rationale is that the therapeutic effects of NSAIDs are achieved by COX-2 inhibition, but that many of the toxic effects, most commonly gastroduodenal injury, result from COX-1 inhibition. 4 COX-2 is also found as a normal constituent of certain tissues such as the brain, kidney and reproductive tract. 1 --------------------------------------------------------------------------------- Cyclooxygenase in Platelets COX 1 is the only isoform of COX present in platelets and is responsible for the synthesis of thromboxane A2 (TxA2) which in turn is responsible for promoting platelet aggregation. Non-specific COX inhibitors such as ASA and NSAIDs inhibit the production of TxA2 via their effect on COX 1 resulting in a decrease in platelet aggregation and a mild bleeding diathesis. Since celecoxib, a cyclooxygenase-2 specific inhibitor, has no inhibitory effect on COX 1 at doses associated with anti-inflammatory and analgesic activity it should have no effect on platelet function. NB : There is not a linear correlation between reduction of thromboxane levels and inhibition of platelet aggregation and bleeding time. Almost complete inhibition of thromboxane is required before changes in aggregation and bleeding time occur. This happens with therapeutic doses of NSAIDs but only ~50% inhibition of TXB2 occurs with doses of celecoxib 3-4 x the maximum therapeutic dose. Cyclooxygenases Prostaglandins are produced from arachidonic acid by cyclooxygenases ( COX-1 and COX-2 ). COX-1 is responsible for the baseline levels of prostaglandins while COX-2 produces prostaglandins through stimulation. While COX-1 is located in the blood vessels , stomach and the kidneys , prostaglandin level are induced by COX-2 in scenarios of inflammation . The recent development of COX-2 inhibitors, known as coxibs , allow the circumvention of the negative gastrointestinal effects while effectively reducing inflammation. [ edit ] Function There are currently nine known receptors of prostaglandins on various cell types. Prostaglandins thus act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostaglandins act principally on a subfamily of G protein coupled receptors . Most of these GPCRs are located at the periphery of target cells at the plasma membrane , however, a few exist within the cell at the nuclear envelope . They may also act upon peroxisome proliferator-activated receptors . Prostaglandins have a wide variety of actions but most cause muscular constriction and mediate inflammation. Other effects include calcium movement, hormone regulation and cell growth control. Thromboxane is created in platelets and causes vascular constriction and platelet aggregation. Prostacyclin comes from cells in the blood vessel walls and is antagonistic to thromboxane
Arachidonic acid is a polyunsaturated fatty acid , one of the essential fatty acids required by most mammals. It is present in the membranes of the body's cells , and is a precursor in the production of eicosanoids : the prostaglandins , thromboxanes , prostacyclin and the leukotrienes . A prostaglandin is any member of a group of lipid compounds that are derived from fatty acids and have important functions in the animal body. They are mediators and have a variety of strong physiological effects; although they are technically hormones they are rarely classified as such. There are two pathways for metabolism of arachidonic acid to prostaglandins, mediated by COX-1 and COX-2. COX-1 is constitutive and is responsible for the production of prostaglandins that protect the GI tract and maintain normal platelet function. COX-2 controls the production of prostaglandins that mediate inflammation and pain. 1,2 NSAIDs inhibit both COX-1 and COX-2 and are non-specific in their mode of action, controlling pain and inflammation but also causing characteristic adverse effects. 3 New strategies have focused on the development of therapeutic agents with pharmacological activity based on specific inhibition of COX-2. 3 The rationale is that the therapeutic effects of NSAIDs are achieved by COX-2 inhibition, but that many of the toxic effects, most commonly gastroduodenal injury, result from COX-1 inhibition. 4 COX-2 is also found as a normal constituent of certain tissues such as the brain, kidney and reproductive tract. 1 --------------------------------------------------------------------------------- Cyclooxygenase in Platelets COX 1 is the only isoform of COX present in platelets and is responsible for the synthesis of thromboxane A2 (TxA2) which in turn is responsible for promoting platelet aggregation. Non-specific COX inhibitors such as ASA and NSAIDs inhibit the production of TxA2 via their effect on COX 1 resulting in a decrease in platelet aggregation and a mild bleeding diathesis. Since celecoxib, a cyclooxygenase-2 specific inhibitor, has no inhibitory effect on COX 1 at doses associated with anti-inflammatory and analgesic activity it should have no effect on platelet function. NB : There is not a linear correlation between reduction of thromboxane levels and inhibition of platelet aggregation and bleeding time. Almost complete inhibition of thromboxane is required before changes in aggregation and bleeding time occur. This happens with therapeutic doses of NSAIDs but only ~50% inhibition of TXB2 occurs with doses of celecoxib 3-4 x the maximum therapeutic dose. Cyclooxygenases Prostaglandins are produced from arachidonic acid by cyclooxygenases ( COX-1 and COX-2 ). COX-1 is responsible for the baseline levels of prostaglandins while COX-2 produces prostaglandins through stimulation. While COX-1 is located in the blood vessels , stomach and the kidneys , prostaglandin level are induced by COX-2 in scenarios of inflammation . The recent development of COX-2 inhibitors, known as coxibs , allow the circumvention of the negative gastrointestinal effects while effectively reducing inflammation. [edit] Function There are currently nine known receptors of prostaglandins on various cell types. Prostaglandins thus act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostaglandins act principally on a subfamily of G protein coupled receptors. Most of these GPCRs are located at the periphery of target cells at the plasma membrane, however, a few exist within the cell at the nuclear envelope. They may also act upon peroxisome proliferator-activated receptors. Prostaglandins have a wide variety of actions but most cause muscular constriction and mediate inflammation. Other effects include calcium movement, hormone regulation and cell growth control. Thromboxane is created in platelets and causes vascular constriction and platelet aggregation. Prostacyclin comes from cells in the blood vessel walls and is antagonistic to thromboxane