Early inflammatory response of knee ligaments to prolotherapy in a rat model

Abstract

Prolotherapy is an alternative injection-based therapy for chronic musculoskeletal pain. Three different proliferants, D-glucose (dextrose), phenol-glucose-glycerine (P2G), and sodium morrhuate, used in prolotherapy are hypothesized to strengthen and reorganize chronically injured soft tissue and decrease pain through modulation of the inflammatory process. Our hypothesis is that commonly used prolotherapy solutions will induce inflammation (leukocyte and macrophage infiltration) in medial collateral ligaments (MCLs) compared to needlestick, saline injection, and no-injection controls. MCLs of 84 Sprague-Dawley rats were injected one time at both the tibial and femoral insertions. Immunohistochemistry (IHC) was used to determine the inflammatory response at three locations (tibial and femoral insertions and midsubstance) 6, 24, and 72 h after dextrose injection compared to saline-and no-injection controls and collagenase (positive control) (n ¼ 4). qPCR was used to analyze gene expression 24 h postinjection (n ¼ 4). Sodium morrhuate, P2G, and needlestick control were also investigated after 24 h (n ¼ 4). In general, inflammation (CD43þ, ED1þ, and ED2þ cells) increased after prolotherapy injection compared to no-injection control but did not increase consistently compared to saline and needlestick control injections. This response varied by both location and proliferant. Inflammation was observed at 6 and 24 h postinjection but was resolved by 72 h compared to no-injection controls (p < 0.05). CD43þ leukocytes and ED2þ macrophages increased compared to needlestick and saline-injection control, respectively, 24 h postinjection (p < 0.05). Prolotherapy injections created an inflammatory response, but this response was variable and overall, not uniformly different from that caused by saline injections or needlestick procedures. ß

Dextrose and Morrhuate Sodium Injections (Prolotherapy) for Knee Osteoarthritis: A Prospective Open-Label Trial

“…23 Proposed biological mechanisms of action have been reviewed. 6 Dextrose injections may stimulate healing of chronically injured intra-and extraarticular tissue 27 ; animal model studies reported increased inflammatory markers 28 and enlarged cross-sectional area in medial collateral ligaments compared to saline injections ( p < 0.05). 29 Morrhuate sodium is a sclerosing agent reported to produce a robust inflammatory response 28 and stronger medial collateral ligaments in animal models.…”

Dextrose Prolotherapy for Knee Osteoarthritis: A Randomized Controlled Trial

“…increased infl ammatory markers 30 and signifi cantly enlarged cross-sectional area in medial collateral ligaments. 31 The potential of prolotherapy to stimulate release of growth factors favoring soft tissue healing 11,32 and a positive neural effect 33 have also been suggested.…”

Association between High Endocardial Unipolar Voltage and Improved Left Ventricular Function in Patients with Ischemic Cardiomyopathy

“…This supports the idea that the needle alone might be all that is required to stimulate inflammation and perhaps to promote angiogenesis. 20 In addition, there is some evidence that direct manipulation of the myocardial surface, most notably with transmyocardial laser therapy, can lead to improvement in cases of angina, 21,22 possibly through the stimulation of angiogenesis. In a similar fashion, intramyocardial needle manipulations (for either mapping or injections) might stimulate the myocardial surface directly and thereby promote the release of stromal cell-derived factor-1 23 and the stimulation of growth factors, such as vascular endothelial growth factor and other signaling molecules.…”