Palmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivity

Abstract

Chronic widespread pain (CWP) is a complex condition characterized by central hyperexcitability and altered descending control of nociception. However, nociceptive input from deep tissues is suggested to be an important drive. N-Acylethanolamines (NAEs) are endogenous lipid mediators involved in regulation of inflammation and pain. Previously we have reported elevated levels of the 2 NAEs, the peroxisome proliferator-activated receptor type-α ligand N-palmitoylethanolamine (PEA) and N-stearoylethanolamine (SEA) in chronic neck/shoulder pain (CNSP). In the present study, the levels of PEA and SEA in women with CWP (n=18), CNSP (n=34) and healthy controls (CON, n=24) were investigated. All subjects went through clinical examination, pressure pain threshold measurements and induction of experimental pain in the tibialis anterior muscle. Microdialysis dialysate of the trapezius was collected before and after subjects performed a repetitive low-force exercise and analyzed by mass spectrometry. The levels of PEA and SEA in CNSP were significantly higher post exercise compared with CWP, and both pre and post exercise compared with CON. Levels of both NAEs decreased significantly pre to post exercise in CWP. Intercorrelations existed between aspects of pain intensity and sensitivity and the level of the 2 NAEs in CWP and CNSP. This is the first study demonstrating that CNSP and CWP differ in levels of NAEs in response to a low-force exercise which induces pain. Increases in pain intensity as a consequence of low-force exercise were associated with low levels of PEA and SEA in CNSP and CWP. These results indicate that PEA and SEA have antinociceptive roles in humans.

Identification of Lipid Mediators in Peripheral Human Tissues Using an Integrative In Vivo Microdialysis Approach

“…The perfusion fluid consisted of Ringer-acetate solution from Baxter Medical (Kista, Sweden) containing 3mM glucose, 0.5mM lactate. The CMA 107 MD pump was used at a flow rate of 5 µL/min [25,26].…”

“…Sampling of dialysate from trapezius muscle was accomplished on a 39 year old healthy male as previously described [26]. The subject was instructed not to drink any beverages with caffeine, not to smoke on the day of MD and to avoid NSAID medication the week before the experiment.…”

“…Zoerner et al have analyzed levels in abdominal adipose tissues in healthy males [24]. We have previously investigated levels of PEA and SEA from the interstitial fluid of trapezius muscle in women with chronic pain conditions compared to healthy controls [25,26].…”

“…We have previously investigated the relative recovery of radiolabeled AEA, PEA and 2-AG in an in vitro study (PEA data published) [26] (AEA and 2-AG unpublished data). In that study liquid scintillation was used for measurements of the lipids.…”

The Role of Palmitoylethanolamide, an Autacoid, in the Symptomatic Treatment of Muscle Cramps: Three Case Reports and Review of Literature

“…PEA can be synthesized in muscle tissue; such synthesis seems be disturbed in fibromyalgia [15]. Although the pathophysiology of muscular cramps remains poorly understood, the pleiotropic lipid autacoid PEA might play a role in stabilizing overactive muscles giving rise to cramping during the night [16]. One of the mechanisms of action for PEA's anti-cramp activity might be its agonistic action at the TRPV1 receptor [17].…”