Dear Pain Matters blog readers,
Chronic Pain and Anti-TNF Drug Therapy
Infliximab and other selective anti-TNF drugs have been used to treat Lumbar Radicular Pain including severe Sciatica, Rheumatoid Arthritis, and Crohn’s disease (refer to first 8 papers in References)….and more recently, for Complex Regional Pain Syndrome (CRPS) (refer to all remaining References).
Complex Regional Pain Syndrome (CRPS) and Anti-TNF Drug Trial
Several European studies showed promising results following anti-TNF drug (Infliximab) trials in CRPS patients.
(1) Infliximab Treatment for 2 CRPS Patients –
In the 1st Infliximab paper, pain decreased in 2 CRPS patients.
– 1st Patient (Female, 50): Chronic CRPS, Duration ~ 5 years
– 2nd Patient (Female, 55): Acute CRPS, Duration ~ 2 months, caused by left arm Colles’ fracture
Blister fluid from the CRPS limbs of both patients showed significant reductions in localised tumor necrosis factor-alpha (TNF) and IL-6 following Infliximab treatment.
More importantly (to the 2 patients anyway), there were:
– Reduced pain;
– Decreased vascular disturbances;
– Less swelling/edema;
– Enhanced motor function; and
– Improved symptoms (Huygen et al, 2004).
(2) Infliximab Treatment for 1 CRPS Patient –
In the 2nd Infliximab paper, pain decreased in 1 patient with acute CRPS. Specifically, a female patient (62) with acute CRPS for 3 months, caused by left hand Colles’ fracture, showed near-complete remission following Infliximab treatment for 8 weeks (Bernateck et al, 2007).
(3) Infliximab Trial for CRPS (7 Cases, Plus Placebo Group) –
Six (6) CRPS patients were treated with Infliximab, while another 7 CRPS patients were given placebo. There was greater reduction in TNF levels in the Infliximab-treated patients (compared to placebo). However, for various reasons, this study was discontinued (Dirckx et al, 2013; Nederlands Trial Register 449 ISRCTN 75765780).
(4) Perispinal Etanercept (A Back Pain Patient) –
The Institute of Neurological Recovery in Florida published an 8-minute YouTube on 25/11/2009 of a female patient with constant and severe back and leg pain for 2 years. Several minutes after a single dose of perispinal Etanercept, she enjoyed pain relief and leg movement.
‘Immediate relief after 2 years of severe constant pain 480p’
More research into anti-TNF drug treatment for CRPS is warranted. Such studies should confirm whether localised TNF levels are elevated in CRPS-affected limbs in the first place. If yes, analysis is necessary whether any anti-TNF drug treatment leads to a significant reduction in these elevated localised TNF levels, and if yes, whether this is also accompanied by reduced pain (etc). Induced skin blisters or skin biopsies may be necessary to confirm localised TNF levels in CRPS-affected limbs, both ‘before’ and ‘after’ anti-TNF drug treatment.
NOTE: If localised TNF levels are already low to begin with (prior to anti-TNF drug treatment), anti-TNF drug treatment is (likely) not justified.
Possible adverse effects also need to be considered prior to anti-TNF drug treatment.
Wishing all pain patients less pain,
PS YOU DON’T HAVE TO READ THE FOLLOWING UNLESS YOU ARE VERY INTERESTED IN SCIENCE –
POSSIBLE MECHANISMS OF ANTI-TNF DRUG THERAPY IN CRPS NERVE PAIN
Anti-TNF drugs (e.g. Infliximab, Etanercept) are TNF monoclonal antibodies that selectively block TNF, hence limiting the pro-inflammatory process.
The reduction of TNF and other pro-inflammatory mediators (via anti-TNF drug therapy, or otherwise) may alleviate certain painful symptoms in CRPS and other nerve pain conditions.
Ongoing trials are warranted including analysis of side effects.
For further details, please refer to 24-page Review Paper by Sabina Walker and Prof. Peter Drummond. In particular, please see pages 1790 – 1791, plus related references on page 1804 (listed below).
Anti-TNF Drug Therapy For Lumbar Radicular Pain Including Severe Sciatica, Rheumatoid Arthritis, and Crohn’s disease
(1) Karppinen et al; Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica. Spine 2003;28:750–4.
(2) Manning; New and emerging pharmacological targets for neuropathic pain. Curr Pain Headache Rep 2004;8:192–8.
(3) Korhonen et al; The treatment of disc-herniation-induced sciatica with infliximab: One-year follow-up results of FIRST II, a randomized controlled trial. Spine 2006;31:2759–66.
(4) Burnett, Day; Recent advancements in the treatment of lumbar radicular pain. Curr Opin Anaesthesiol 2008;21:452–6.
(5) Cohen et al; Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology 2009;110:1116–26.
(6) Lipsky et al; Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 2000;343:1594–602.
(7) Emery, Buch; Treating rheumatoid arthritis with tumor necrosis factor alpha blockade. BMJ 2002; 234:212–213.
(8) Blam et al; Integrating anti-tumor necrosis factor in inflammatory bowel disease: current and future perspectives. Am J Gastroenterol 2001;96:1977–1997.
Anti-TNF Drug Therapy For Complex Regional Pain Syndrome (CRPS)
(9) Huygen et al. Successful treatment of CRPS 1 with anti-TNF. J Pain Symptom Manage 2004;27:101–3.
(10) Bernateck et al. Successful intravenous regional block with low-dose tumor necrosis factor-a antibody infliximab for treatment of complex regional pain syndrome 1. Anesth Analg 2007;105:1148–51.
(11A) Dirckx, Groeneweg, Wesseldijk, Stronks, Huygen; Report of a Preliminary Discontinued Double-Blind, Randomized, Placebo-Controlled Trial of the Anti-TNF-α Chimeric Monoclonal Antibody Infliximab in Complex Regional Pain Syndrome; Pain Practice (Nov 2013); 13(8):633–640.
(11B) Nederlands Trial Register 449 ISRCTN 75765780
(12) Sabina Walker, Peter D. Drummond; Implications of a Local Overproduction of Tumor Necrosis Factor-α in Complex Regional Pain Syndrome [Review Paper, 24 pages]; Pain Medicine (Dec 2011), 12 (12), 1784–1807.
In particular, please refer to pages 1790 – 1791, plus related references on page 1804 (also listed above).