Chronic pain after breast cancer surgery.

Breast surgery for cancer is associated with both tissue and nerve damage, and is frequently followed not only by acute, but also by chronic pain, causing significant medical and social morbidity. The nociception of surgery is now recognised to result in postoperative hyperalgesia via changes in central nervous system processing (central sensitisation). Such neuroplasticity is mediated both via humoral (tissue damage leading to inflammation) and neuronal (nerve damage leading to neuropathy) nociceptive inputs. Postoperative hyperalgesia will lead to increased pain, which - together with nerve damage - has recently been linked to subsequent pain chronification in a number of studies. Based on animal studies, it is now accepted that a major mechanism for such pain chronification is the persistence of (abnormal) central sensitisation.

The aim of this study is to investigate the interaction between extended perioperative COX-2 inhibition (starting before surgery and continuing 5 days into the postoperative period) and extended locoregional block (paravertebral block) using local anaesthetics on central sensitisation after breast surgery. This should enable us to gain insight into the relative contributions of humoral (inflammatory) and neuronal (neuropathic) nociceptive inputs to acute postoperative hyperalgesia, persistence of central sensitisation and pain chronification after breast surgery. The defined primary study endpoint is the persistence and extent of central sensitisation one month after breast surgery as measured by quantitative sensory testing. The study will further investigate effects on clinical pain and other outcome measures, and determine their relationship to measures of central sensitisation.

To study the effect of the interaction of cyclooxygenase-2 (COX-2) inhibition (started preoperatively and continued 5 days into the postoperative period) and extended local anaesthetic blockade via paravertebral block on postoperative central sensitisation after breast surgery for malignancy.

1. At formal recruitment before surgery;

2. On leaving recovery unit postoperatively (inpatient; not measures 6-7);

3. 5, 15 days postoperatively (outpatient);

4. 1, 3, 6 and 12 months post-mastectomy (outpatient);

5. 12 months post-mastectomy, we will additionally collect details on.

After informed patient consent, patients will be randomised to either an active or placebo treatment group. On the morning of surgery, the patient will receive oral midazolam premedication (7.5 mg). In the operating theatre, the patients randomised to the active group will receive an i.v. injection of parecoxib 40 mg 30 minutes before the start of surgery. The injection will be repeated 6 hours later. On the evening of the operation day patients will start celecoxib 2 X 200mg/d and continue this scheme until the morning of the fifth postoperative day. The placebo group will receive placebo injections and tablets according to the same regime. As the medication will be blinded, neither observers nor persons involved in patient management nor observers will be aware of which group the patients are in.