From Acute to Chronic PainChronic Post Surgical Pain Prevention or Treatment
Xavier Capdevila M.D.,Ph.D.Head of Department
Department of Anesthesiology and Critical Care MedicineLapeyronie University Hospital and Montpellier School of Medicine
Montpellier , France
Pain physiopathology: are we too simplistics???
SII
Insula (emotivity)
Nucleus accumbens
(awakeness)
Cerebellum (motivation)
Thalamus
SI
Pain physiopathology: complex systems!!!
No BrainNo Pain
Pain physiopathology: are we too simplistics???
ASA 2008, d’après J.Eisenach, RCL 123
Transition … from acute to chronic pain
Transition … from acute to chronic pain
Fonctional Imagery
Many hemispheric regions are activated during painful stimulation, and particularly at the controlateral level (orange areas).
http://www.hopkins-arthritis.som.jmhi.edu/rheumatoid
Pain Imagery…for pain and other goals!!!
Genes, Pain, Analgesia
Zubieta, Science 2003 ; Rakvåg et al, Pain 2005
Génotype COMT et fréquence des allèles chez 207 patients cancéreux
Pharmacologic results for genotypics groups Val158Met (mean ± DS ; a : p = 0,025 ; b : p = 0,03 Val/Val vs Met/Met)
Incidence of genotypeIncidence of
gene allel
Val/Val Val/MetMet/Met
Val Met
N 44 96 67 184 230
Incidence 0,21 0,47 0,32 0,44 0,56
Val/Val(n = 44)
Val/Met(n = 96)
Met/Met(n = 67)
Morphine dose (mg/24 h)a, b 155 (160) 117 (100) 95 (99)
Morphine serum (nmol/L) 119 (199) 86 (88) 78 (72)
M6G serum (nmol/L) 711 (992) 506 (493) 410 (484)
M3G serum (nmol/L) 3 809 (4 436) 2 812 (2 209) 2 536 (2 707)
Val158Met polymorphism of human genom for catechol-O-methyltransferase (COMT) influences morphine consumption in painfull patients
All patients had a continuous popliteal block with 20 ml 0.5% ropivacaine before surgery
Chronic P.O. pain
CRPS 1 after orthopedic surgeries
Post-operative pain chronicisation
surgery n (milliers/an) % SDRC n (milliers/an)
Knee arthroscopy 657 2,3 – 4,0 15,1 – 26,3
Carpal tunel release 366 2,1 – 5,0 7,7 – 18,3
Ankle fracture 257 13,6 35,0
TKR 247 0,8 – 13,0 2,0 – 32,1
Wrist fracture 194 7,0 – 37,0 13,6 – 71,8
Dupuytren surgery 20 4,5 – 40,0 0,9 – 8,0
Total 1741 4,3 – 11,0 74,3 – 191,5
Gooschalk & Raja Anesthesiology 2004
Pain physiopathology : the peripheral inflammation!
Neuropathic pain = neuro-immune disorder ?
ASA 2008, d’après J.Eisenach, RCL 123
Pain physiopathology: central inflammation and sensitization
http://www.hopkins-arthritis.som.jmhi.edu/rheumatoid
Neuropathic pain (pain without stimulus) implies a lower thresholds and involves the same pathway as Schwann cells, cells from dorsal root ganglia, theimmune system, microglia and spinal astrocytes.
Glial cells are the inflammatory cells of the central nervous system
abatacept , etanercept…infliximab, tanezumab, natazulimab…
………from acute to chronic pain
Pain Physiopathology: central inflammation
From acute pain to chronic pain: TNF antibodies
ASA 2008, d’après Shelton et al, A-1539
NGF (nerve growth factor) : acute/chronic pain
tanezumab --> monoclonal Antibody anti-NGF
Useful in Rheumatology (knee), ½ life: 21 days
No fixation of NGF on TrkA receptor
(tropomyosin kinase A)
Significant decrease of pain scores
Less efficacy if intraoperative administration
Acute pain/ Chronic pain: Atb anti-NGF
Plantar incision model
Intraperitonea/IV injection 16h before incision
Pain physiopathology: non-NMDA receptors
TNF in the DRG Transport of TNF
TNF Expression along the saphenous nerve
Paw circumference
TNF alpha at the surgical site
Eisenach Reg Anesth Pain Med 2006
Postoperative pain and chronic pain related?Postoperative pain and chronic pain related?
M De Kock et al , Pain 2001 P Lavand’homme et al, Anesthesiology 2005
Colectomies : midline xyphopubic incision– i.v. ketamine : antihyperalgesic dose – then i.v. sufentanil-lidocaïne-clonidine– or EA sufentanil-bupivacaïne-clonidine
• G1 : i.v.-i.v.• G2 : i.v.-EA• G3 : EA-EA • G4 : EA-i.v.
– VAS / cough, hyperalgesia (von Frey hairs)– Analgesic consumption– Follow up 2 weeks, 6 months, 1 year
The effect of three different analgesia techniques on long-term post-thoracotomy pain
Sentürk et al. Anesth Analg 2001;94:11-5
*
* P < 0.05 vs. IV PCA
*
Chronic postsurgical pain…
Anesth Analg 2005;101:1427-32.
Treatment: gabapentin +EMLA cream + ropi in thebrachial plexus and in the third to the fifth intercostalnerves
Gabapentin: 400 mg started the evening before surgery and for 8 days (400 mg x 4).EMLA cream for 3 days.
*
*
* P < 0.05 vs. control
All patients received a continuous brachial plexus block with ropivacaine 0;375%
PP: phantom painSP: stump pain
Research of the optimal local analgesia: capsaïcin and TRPv1 receptors
CRPS 1 and orthopedic surgeries
Does a PNB modifie the evolution?
•Dupuytren Surgery
4,4% to 40% of postoperative CRPS 1 Sennwald J Hand Surg 1990 Prosser J Hand Ther 1996 Interest of PNBs Reuben Anesth Analg 2006
300 patients, Dupuytren surgery GA n : 100 Axillary block n : 96 IVRA lido n : 48 IVRA lido + clo n : 50
GA 24% Axillary block 5%IVRA lido 25 % IVRA lido + clo 6%
% CRPS 1 p<0,01
+ for Axillary block : tourniquet tolerance and postoperative analgesia
Pain evaluation after PNB
Iliac crest graft for orthopaedic surgery
The TAP block Chiono J, Capdevila X et al RAPM 2010
Pain chronicisation: 8% at 3 months