From Acute to Chronic Pain Chronic Post Surgical Pain Prevention or Treatment Xavier Capdevila M.D.,Ph.D. Head of Department Department of Anesthesiology and Critical Care Medicine Lapeyronie 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 Brain No Pain Pain physiopathology: are we too simplistics???

ASA 2008, d’après J.Eisenach, RCL 123 Transition … from acute to chronic pain

Fonctional Imagery Many hemispheric regions are activated during painful stimulation, and particularly at the controlateral level (orange areas).

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 genotype Incidence of gene allel Val/ValVal/Met Met/Me t ValMet N Incidence0,210,470,320,440,56 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 surgeryn (milliers/an)% SDRCn (milliers/an) Knee arthroscopy6572,3 – 4,0 15,1 – 26,3 Carpal tunel release3662,1 – 5,0 7,7 – 18,3 Ankle fracture257 13,6 35,0 TKR2470,8 – 13,0 2,0 – 32,1 Wrist fracture1947,0 – 37,013,6 – 71,8 Dupuytren surgery204,5 – 40,0 0,9 – 8,0 Total 17414,3 – 11,074,3 – 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

Neuropathic pain (pain without stimulus) implies a lower thresholds and involves the same pathway as Schwann cells, cells from dorsal root ganglia, the immune 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 DRGTransport 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?

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: Treatment: gabapentin + EMLA cream + ropi in the brachial plexus and in the third to the fifth intercostal nerves 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 pain SP: 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 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