ketamine's efficiency in the treatment of chronic pain: kynurenin pathway

Conditions: Neuralgia; Chronic Pain; Inflammation

Summary: the kynurenine pathway is involved in hyperalgesia. this pathway is activated by inflammation. ketamine would interact with the kynurenine pathway and inflammation. our working hypotheses are: the clinical effects of ketamine on neuropathic pain are greater in the presence of systemic inflammation and the mechanism of action involves an interaction on the kynurenine pathway. study design: interventional randomized placebo-controlled clinical trial. ￼main goals: 1. to show a better clinical efficacy of ketamine in chronic pain in patients with an inflammatory component. 2. explore the anti-inflammatory activity of ketamine through the kynurenine pathway.

the kynurenine pathway is involved in hyperalgesia. this pathway is activated by inflammation. ketamine would interact with the kynurenine pathway and inflammation. our working hypotheses are: the clinical effects of ketamine on neuropathic pain are greater in the presence of systemic inflammation and the mechanism of action involves an interaction on the kynurenine pathway. study design: interventional randomized placebo-controlled clinical trial. ￼main goals: 1. to show a better clinical efficacy of ketamine in chronic pain in patients with an inflammatory component. 2. explore the anti-inflammatory activity of ketamine through the kynurenine pathway. population adult, medullary injured (bm), with chronic neuropathic pain (dn). 4 groups: bm with dn with bedsore ketamine group versus placebo group bm with dn without bedsore group ketamine versus placebo group intervention ketamine infusion 1 mg / kg ivse over two hours versus nacl perfusion 0.9% ￼ primary judgment criterion decrease by more than 30% the intensity of neuropathic pain evaluated at the moment on a numerical scale of 10 points between h0 and h4. comparison of groups two by two. secondary judgment criterions: npsi score (neuropathic pain symptom inventory) at h1, h4, d1, d4, j7 sub score of npsi; h1, h4, j1, j4, j7 depression scale hads (hospital anxiety depression scale) j0, j1, j7 plasma serotonin (5-ht) kynurenine (kyn), indoleamine 2,3-dioxygenase 1 (ido1) activity (kyn / trp ratio), kynurenic acid ( ka) and quinolinic acid (qa), as well as 3 proinflammatory cytokines il-1β, il-6, and tnf-α before perfusion and h4 perfusion. in parallel blood samples will be collected to study the activation of the kynurenine pathway in response to inflammation due to a pressure ulcer.

Eligibility criteria:
inclusion criteria: * adults speaking and understanding french * presenting chronic neuropathic pain as defined by iasp * painful intensity\> or = to 6/10 during the week preceding the inclusion - medullary lesion, whatever the origin (traumatic, degenerative, tumoral, postoperative), responsible for paraplegia in a chronic state. * able to give informed consent, after clear, fair and appropriate information * having given their consent by a written consent signature. exclusion criteria: * hypersensitivity to ketamine or any of its components * participation in another interventional trial, or participation in another trial. * patient unable to give consent. * pregnancy or breastfeeding * refusal to sign the consent * cardiovascular diseases associated in particular with disorders of rhythm and severe cardiac insufficiency, coronary insufficiency, discovered on examination, on ecg or by biological balance or known. - unstabilized hta\> 180/100 mmhg * severe hepatic and / or renal hepatic insufficiency.

Keywords: ketamine chronic pain neuropathic pain kynurenine kynurenine pathway bedsores anti-inflammatory ulcer pressure