Breast Cancer, Surgery
Conditions
Keywords
polyamines, pain, breast cancer, mastectomy, post operative pain
Brief summary
After surgery, sensitization and hyperexcitability of central nervous system result in acute and long lasting postoperative pain. It has been shown that N-methyl-D-aspartate (NMDA) receptors antagonist (such as ketamine) prevent this adverse neuroplasticity and potentiate analgesic drugs efficacy. Polyamines (putrescine, spermidine, spermine) are essential components of cells functioning and are also known as allosteric modulators of NMDA receptors. In animal studies, polyamine-free diet has confirmed these antinociceptive properties. This research aims at evaluating anti hyperalgesic properties of polyamine-free diet in women operated on breast cancer versus kétamine
Detailed description
This multicentric, single blind study will enrol 160 women (18-75 years old) operated on tumorectomy and adenectomy (T1, T2, T3, N0, N1, M0) for breast cancer. Patients will be randomly assigned in a 2x2 factorial plan : Group 1 = control (n = 40) ; group 2 = ketamine group administered during and 48 hours after a standardized anesthesia (n = 40) ; group 3 = polyamine-free diet, 1 week and 72 hours after surgery (n = 40) ; group 4 : ketamine + polyamine-free diet (n = 40). The amount of morphine for the 24 first postoperative hours will be compared between each group as well as pain score, allodynia (Von Frey filaments) and hyperalgesia (algometer). Chronic pain occurrence (post-mastectomy pain syndrome) will be evaluated at 3 and 6 months using adequate questionnaire ( analgesic scale). Diet observance will be controlled preoperatively by a dosage of polyamines in circulating red cells blood. Polyamines deprivation and ketamine ability to reduce postoperative pain will be compared (isobolographic method). Anti-hyperalgesic properties of ketamine have already been demonstrated in urologic, orthopaedic and abdominal surgery. In case of additive or synergistic effect of a polyamine deprivation such a strategic could be helpful to achieve better postoperative rehabilitation in reducing chronic pain after surgery.
Interventions
BEHAVIORALpolyamine-free diet
Polyamine-free diet in the 7 days befor surgery
DRUGKetamine or placebo
Peroperative and post operative (48h) ketamine injection
Sponsors
Ministry of Health, France
Insurance CNP foundation
University Hospital, Bordeaux
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Breast cancer (T1, T2, T3, N0, N1, M0) * Age : 18 - 75 * Asa 1-3 * left or right tumorectomy with complete lymphadenectomy * left or right complete mastectomy with complete lymphadenectomy * complete lymphadenectomy within one week following simple tumorectomy * informed consent signed
Exclusion criteria
* inflammatory tumor requiring pre-operative radiotherapy * previous history of total mastectomy or partial contralateral mastectomy * chronic inflammatory disease treated by corticoids or NSAI * chronic analgesic treatment * anti-arrhythmic or anti-epileptic treatments * morphinic treatment during the 7 days before surgery * excessive alcohol consumption or addiction * ketamine or neomycin contra-indication * severe cardiovascular disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Morphine requirement | for the 24 postoperative hours |
Secondary
| Measure | Time frame |
|---|---|
| Allodynia measurements | inclusion, 1, 2, 4 and 7 ddays after surgery |
| Hyperesthesia measurements | inclusion, 1, 2, 4 and 7 ddays after surgery |
| Pain intensity for the 4 days (and possibly at 7th day if the patient is still hospitalized) after surgery | 4 days |
| Late allodynia and/or hyperesthesia | 6 months |
| safety of treatment | Along each patient folow-up |
| Chronic pain incidence | 3 and 6 months |
Countries
France
Outcome results
None listed