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