Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models

Guo, Wei; Chu, Yu Xia; Imai, Shoichi; Yang, Jia Le; Zou, Shiping; Mohammad, Zaid; Feng, Wei; Dubner, Ronald; Ren, Ke

doi:10.1177/1744806916658043

Cited by 30 publications

(38 citation statements)

References 41 publications

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“…Bone marrow derived stem cells have been examined in a number of applications for their ability to modulate neuroinflammation. They have been delivered via intra-ganglionic, intra-spinal, intra-brain, intra-muscular and intrathecal injection as well as through intravenous infiltration [19,[21][22][23][24][25][26][27][28][29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Orthobiologic Supplementation Improves Clinical Outcomes Following Lumbar Decompression Surgery

Kamson¹,

Smith

2020

J Clin Med Res

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Background: Endoscopic-assisted lumbar decompression is a minimally invasive spine surgery which has been touted to reduce collateral tissue damage, incisional pain, recovery time and complications. Residual back or leg pain and recurrent herniation are commonly reported post-operative outcomes. It has been suggested that injecting orthobiologics like cryopreserved amniotic-derived products (ADPs) and bone marrow aspiration (BMA) into the surgery site would have additional benefit on patient outcomes. This is a Western Institutional Review Board (WIRB)-approved level 1, randomized controlled trial of prospectively collected patient demographic and outcomes data for endoscopic-assisted lumbar decompression surgery. The primary goal of this study was to compare patient outcomes of orthobiologic supplementation during endoscopic-assisted lumbar decompression surgery. Methods: Following WIRB approval, 269 patients underwent lumbar endoscopic-assisted decompressive surgery between January 2011 and October 2017. Patients were randomized to receive ADP, BMA, both, or no supplementation (control group). Outcomes were measured by post-operative questionnaires (visual analog scale (VAS), Oswestry disability index (ODI), 36-item short-form health survey (SF-36)) over 12 months. Results: Mean VAS-leg for either BMA or ADP group displayed statistically significant improvements at 2 weeks (3.55 vs. 4.77, P = 0.002), 6 months (2.34 vs. 3.37, P = 0.026), and 9 months (2.18 vs. 3.57, P = 0.01) compared to no supplementation group (control group). Similarly, improvements in mean VAS-back were significant at 2 weeks (3.98 vs. 5.01, P = 0.011), 2 months (3.22 vs. 3.93, P = 0.04), 9 months (2.38 vs. 4.11, P = 0.004), and 12 months (2.23 vs. 3.58, P = 0.011) compared to no supplementation group (control group). There were statistically significant differences in the ODI (2 weeks, 42.19 vs. 31.11, P = 0.014) and SF-36 (4 months, 85 vs. 63, P = 0.043 for ADP only), but these differences did not subsist over time. Two patients (one control, one ADP) re-herniated at the same level. Conclusions: Orthobiologic BMA and ADP resulted in improved pain control during early post-operative periods.

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Section: Discussionmentioning

confidence: 99%

Orthobiologic Supplementation Improves Clinical Outcomes Following Lumbar Decompression Surgery

Kamson¹,

Smith

2020

J Clin Med Res

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“…In a variety of neuropathic pain models, BMSCs were injected directly into the lesion site [ via intraganglionic ( 41 ), intraspinal ( 13 , 42 , 43 ), intrabrain ( 44 ), intramuscular ( 11 , 45 , 46 ), intrathecal injection ( 14 , 47 – 49 ), or sytemic intravenous administration ( 11 , 50 – 52 )]. For example, intravenous injection of BMSCs reduced mechanical allodynia and thermal hyperalgesia in rodent chronic constriction injury (CCI) models of the sciatic ( 50 ) and infraorbital nerve ( 11 , 52 ), as well as in spared nerve injury (SNI) models ( 51 ). Intramuscular injection of BMSCs reduced mechanical allodynia and cold pain in an STZ-induced diabetic model ( 45 , 46 ) and also in an infraorbital nerve CCI model of orofacial pain ( 11 ).…”

Section: Bmscs Produce Pain Relief In Animal Modelsmentioning

confidence: 99%

Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain

2017

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Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS) plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG)], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain), and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL)-1β, IL-6, CCL2, and CXCL1]. Recent studies suggest that bone marrow stem cells or bone marrow stromal cells (BMSCs) produce powerful analgesic effects in animal models of inflammatory pain, neuropathic pain, and cancer pain. We recently demonstrated that intrathecal injection of BMSCs resulted in a long-term relief of neuropathic pain for several weeks after peripheral nerve injury. Strikingly, this analgesic effect is mediated by the anti-inflammatory cytokine transforming growth factor beta secreted from BMSCs. Additionally, BMSCs exhibit potent modulation of neuroinflammation, by inhibiting monocyte infiltration, glial activation, and cytokine/chemokine production in the DRG and spinal cord. Thus, BMSCs control chronic pain by regulation of neuroinflammation in the PNS and CNS via paracrine signaling. In this review, we discuss the similar results from different laboratories of remarkable anti-nociceptive efficacy of BMSCs in animal and clinical studies. We also discuss the mechanisms by which BMSCs control neuroinflammation and chronic pain and how these cells specifically migrate to damaged tissues.

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“…To address this issue, we analyzed biting parameters during prolonged myofascial pain induced by ligation injury of the masseter muscle tendon (TL) in mice. Utilizing bone marrow stromal cells (BMSCs) that have been shown to attenuate persistent pain [17][18][19][20], we show that reduced bite force after TL was improved after infusion of BMSCs.…”

Section: Introductionmentioning

confidence: 99%

Voluntary biting behavior as a functional measure of orofacial pain in mice

Guo

Zou

Mohammad

et al. 2019

Physiology & Behavior

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Introduction: Pain-related behavior secondary to masticatory function can be assessed with the rodent bite force model. A reduction of the bite force has been shown to be related to pain associated with the masseter muscle and jaw activity, while an increase in bite force suggests improvement of muscle function and less pain. To evaluate the usefulness of the bite force measure in studying long-lasting orofacial pain we analyzed biting parameters during prolonged myofascial pain induced by ligation injury of the masseter muscle tendon (TL) in mice. Methods: C57BI/6 mice were habituated to bite at a pair of aluminum plates attached to a force displacement transducer. The transduced voltage signals were amplified and converted to force through calibration with a standard weight set. Voluntary biting behavior was recorded for 100 seconds/session and those with bite forces ≥ 980 mN were analyzed. Nociception was also verified with von Frey, conditioned place avoidance (CPA) tests and mouse grimace scale. Persistent orofacial pain was induced with unilateral ligation of one tendon of the masseter muscle (TL). Results: To reduce interference of random bites of smaller forces, the top 5 or 15 bite forces (BF5/15) were chosen as a measure of masticatory function and related to pain behavior. Both male and female mice exhibited similar BF5/15. For the first nascent test of all mice, mean bite force was significantly and positively correlated with the body weight. However, this correlation was less clear in the latter tests (2-8 w). TL induced a reduction of BF5/15 that peaked at 1 w and returned to the baseline within 3 w. The von Frey and CPA tests indicated that mechanical

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Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models

Cited by 30 publications

References 41 publications

Orthobiologic Supplementation Improves Clinical Outcomes Following Lumbar Decompression Surgery

Orthobiologic Supplementation Improves Clinical Outcomes Following Lumbar Decompression Surgery

Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain

Voluntary biting behavior as a functional measure of orofacial pain in mice

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