REV_Leaflet_Pain_210x275mm.qxp_Mise en page 1 30/08/2017 17:26 Page2

Scientist-to-Scientist

PAIN MODELS

PORSOLT HAS AN EXTENSIVE PORTFOLIO OF SERVICES SUPPORTING DRUG

DISCOVERY AND DEVELOPMENT. THE DOMAINS OF ACUTE AND CHRONIC

PAIN AND INFLAMMATION ARE ACTIVE AREAS OF RESEARCH AT PORSOLT

MATCHING THE NEEDS OF THE INDUSTRY.

PORSOLT REMAINS COMMITTED TO MAINTAINING A RECOGNIZED EXPERTISE

IN THESE IMPORTANT THERAPEUTIC AREAS BY CONTINUING TO EXPAND ITS

BROAD PAIN CAPABILITIES. 7 1 0 2 r e b m e t p e S

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PAIN MODELS Acute Pain Neuropathic Pain • Acute nociception in rodents: • Bennett (CCI) model of neuropathic pain in the rat: PINCHMETER | HOT PLATE | TAIL FLICK | COLD PLATE Neuropathic pain develops over the 7 days following chronic loose ligation of the sciatic nerve. Several acute pain assays measuring responses to tactile and thermal stimulation are available in rodents. • Chung (SNL) model of neuropathic pain in the rat: Neuropathic pain develops over the 14 days following chronic Classically, the pinchmeter (alternative method to the Randall and tight ligation of the dorsal root nerve (L5-L6). Selitto test) is used to assess tactile hyperalgesia, while the hot plate, cold plate and tail flick tests evaluate thermal hyperalgesia. MEASURE REFERENCE ROUTE EFFECT* SPECIES REFERENCE ROUTE EFFECT n BENNETT | CHUNG IN THE RAT n PINCHMETER Plantar, Cold Plate, Electronic von Frey, Morphine i.p. 4 Mouse/Rat Morphine i.p. 4 Pinchmeter Mouse/Rat Tramadol p.o. 4 Plantar, Cold Plate, n HOT PLATE Electronic von Frey, Pregabalin p.o. 4 Mouse/Rat Morphine p.o., i.p., s.c., i.v.*, i.t.* 4 Pinchmeter Mouse/Rat Paracetamol i.p., p.o. 4 Mouse Tramadol p.o. 4 Plantar, Cold Plate, Mouse Codeine p.o. 4 Electronic von Frey, Tramadol i.p. 4 Pinchmeter n TAIL FLICK Plantar, Cold Plate, Mouse/Rat Morphine p.o., i.p., s.c., i.v.*, i.t.* 4 Duloxetine p.o. 4 Mouse/Rat Tramadol p.o. 4 Pinchmeter Mouse Codeine p.o. 4 Rat Fentanyl s.c. 4 * Positive effects are observed on selected measures ≥ n COLD PLATE Several pain measures can be used: Mouse/Rat Morphine i.p. 4 - Thermal stimulation (heat hyperalgesia or cold allodynia): Mouse/Rat Tramadol p.o. 4 measured using the Hargreaves method or the cold plate Rat Pregabalin p.o. 4 test (4°C), respectively. * In the mouse only - Tactile stimulation (tactile allodynia or tactile hyperalgesia): measured using an electronic von Frey apparatus or a COLD PLATE TEST IN THE RAT (-3°C) pinch meter. 30 ≥ Optional non-evoked pain measures:

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Post-Operative Pain Inflammatory Pain • Brennan model of post-operative pain in the rat: • Inflammatory pain in rodents:

- A longitudinal incision of skin, fascia and muscle of the plantar - FORMALIN (early and late phase) (rat and mouse) aspect of the rat hindpaw is performed under anesthesia. - CAPSAICIN (rat and mouse) Tactile allodynia, tactile hyperalgesia and thermal hyperalgesia - - CARRAGEENAN MODEL (rat and mouse) can be measured as early as 3 hours after surgery and up to 3-4 afterwards. Rats are injected with carrageenan into the lower surface of the right hindpaw and evaluated at least 2 hours later. (1) - Dynamic Weight Bearing (DWB ) evaluation can also be used. - COMPLETE FREUND’S ADJUVANT MODEL (rat and mouse) MEASURE REFERENCE ROUTE EFFECT Rats are injected with CFA into the lower surface of the right hindpaw and evaluated 24 hours later. n BRENNAN IN THE RAT Electronic von Frey, - CHRONIC INFLAMMATORY PAIN Morphine p.o, i.p., s.c. 4 Plantar, Pinchmeter (CFA-induced monoarthritis) (rat) Rats are injected with a suspension of Mycobacterium Electronic von Frey Ibuprofen p.o. 4 butyricum ( Freund's adjuvant) into the tibio-tarsal joint. Electronic von Frey, Testing phase can be performed 7 and/or 14 days Anandamide i.p. 4 Plantar after induction - OSTEOARTHRITIS: MIA MODEL (rat) SNB Electronic von Frey, Bupivacaine (Sciatic Nerve 4 Monosodium iodoacetate (MIA) is injected through Plantar, Pinchmeter Block) the infra patellar ligament into the joint space of one knee. Testing phase is performed 14 days after induction 120 Brenn an mo del - SURGICAL OSTEOARTHRITIS (guinea-pig) (anterior cruciate 100 ligament ACL transection combined to meniscal lesion) ** *

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PAIN MODELS Visceral Pain Inflammation

• Acetic acid or Parabenzoquinone-induced • YEAST HYPERTHERMIA writhing in the mouse: • LPS SEPTIC SHOCK - Animals are injected with acetic acid or parabenzoquinone (i.p.). • AIR POUCH - The number of writhes is counted for 10 minutes, beginning 5 minutes after the injection of reagent substance. • EAR EDEMA

REFERENCE ROUTE EFFECT • ACUTE CARRAGEENAN

n ACETIC ACID–INDUCED WRITHING IN THE MOUSE Morphine p.o., i.p., i.v. 4

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For further information, visit our website www.porsolt.com or contact us at [email protected] Compliance Z.A. de Glatigné • 53940 Le Genest-Saint-Isle, France | Telephone +33 2 43 69 36 07