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Adipose Tissue As Pain Generator in the Lower Back and Lower Extremity

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Adipose Tissue As Pain Generator in the Lower Back and Lower Extremity Lee et al. HCA Healthcare Journal of Medicine (2020) 1:5 https://doi.org/10.36518/2689-0216.1102 Clinical Review Adipose Tissue as Pain Generator in the Lower Back and Lower Extremity: Application in Author affiliations are listed Musculoskeletal Medicine at the end of this article. Se Won Lee, MD ,1 Craig Van Dien, MD ,2 Sun Jae Won, MD, PhD3 Correspondence to: Se Won Lee, MD Abstract Department of Physical Medicine and Rehabilitation Description MoutainView Medical Adipose tissue (AT) has diverse and important functions in body insulation, mechanical protection, energy metabolism and the endocrine system. Despite its relative abundance in Center the human body, the clinical significance of AT in musculoskeletal (MSK) medicine, partic- 2880 N Tenaya Way, 2nd Fl, ularly its role in painful MSK conditions, is under-recognized. Pain associated with AT can Las Vegas, NV 89128 be divided into intrinsic (AT as a primary pain generator), extrinsic (AT as a secondary pain ([email protected]) generator) or mixed origin. Understanding AT as an MSK pain generator, both by mechanism and its specific role in pain generation by body region, enhances the clinical decision-making process and guides therapeutic strategies in patients with AT-related MSK disorders. This article reviews the existing literature of AT in the context of pain generation in the lower back and lower extremity to increase clinician awareness and stimulate further investigation into AT in MSK medicine. Keywords adipose tissue; fat pad; musculoskeletal pain; connective tissue; lipodystrophy; lipoma; obe- sity; lipedema; pain generator Introduction lower extremity, focusing on its pathogenic role Mounting evidence supports the various func- as a pain generator as well as practical diagno- tions of adipose tissue (AT), most notably its sis and management. link to obesity and metabolic dysfunction.1-3 Aside from the impact of obesity on the mus- Distribution, Physiologic Changes culoskeletal (MSK) system, the role of AT in painful MSK conditions is less established. and Mechanical Properties of Historically, AT masses/lipomas were consid- Adipose Tissue ered common pain generators. However, the AT is largely located in subcutaneous regions, high prevalance of asymptomatic lipomas,4,5 followed by visceral regions. Ectopic areas inconsistent responses to local injections and of deposition include bone marrow and the increasing awareness of other neighboring pain retro-orbital, intramuscular, intermuscular generators disputed their reputation in painful and periarticular regions.7 With aging, there is MSK conditions. AT has recently re-entered global redistribution of AT from subcutaneous the focus of MSK clinicians, most notably for to truncal/visceral regions.8 Local redistribution its use in regenerative medicine.6 Moreover, also occurs, as seen in AT on the plantar aspect localization and evaluation with high resolution of the heel and metatarsophalangeal joints.9 In imaging technologies has improved under- addition, aging AT cells undergo cellular senes- standing of AT in other contexts, particularly cence, a process that promotes AT dysfunction pain generation. Therefore, our objective is to through dysregulation of extracellular remod- review the available literature on AT-related eling, inflammation and pathologic angiogene- painful MSK disorders in the lower back and sis.10 www.hcahealthcarejournal.com HCA Healthcare © 2020 HCA Physician Services, Inc. d/b/a Journal of Medicine Emerald Medical Education 257 HCA Healthcare Journal of Medicine AT is a highly expandable connective tissue pain from isolated inflammation of Kager’s fat comprised of adipocytes (lipid-filled cells) pad and nonspecific anterior knee pain related enclosed within collagen-based structures to inflammation of the infrapatellar fat pad.21 (basement membrane and interlobular septa) AT torsion resulting in inflammation and/or and smaller numbers of fibroblasts.11 It protects ischemic necrosis is amongst other proposed the underlying MSK structures, contributes to mechanisms of AT-based pain.22 mechanical stability and resists shear strain.12 Nonetheless, the mechanical integrity of AT Extrinsic Pain Generation varies between individuals and over an individ- Painful MSK conditions can be related to the ual’s lifespan. For example, the stiffness and interaction of AT with surrounding structures, thickness of heel AT was found to be higher in i.e., extrinsic pain generator. Lipomas, for ex- overweight and obese individuals as compared ample, are AT masses that can arise from any to normal-weight individuals.12 This discovery is location where fat is normally present. Local partly explained by increased fibrosis, a process pain in lipomas can result from irritation of a that limits the ability of adipocytes to expand.13 fascial layer or other neighboring structures, Increased stiffness can also reflect a degenera- such as bursa and nerve.23 If nerve irritation oc- tive process, as repetitive microtrauma reduces curs, distant pain (either radiating or referred) water content and elastic fibrous tissues.13-15 can be experienced.24 The pain characteristics Furthermore, septal hypertrophy and frag- and presentation of painful fat pads/symp- mented elastic fibers in heel AT occurs with ag- tomatic lipoma will vary based on the body 12 ing. These changes can negatively impact the region and surrounding structures. (Table 1) As mechanical properties of AT and consequently another example, increased adiposity can cause its functions in shock absorption and resistance tendinopathy due to direct mechanical loading to compressive and sheer forces of gait.12 and biochemical alterations caused by systemic dysmetabolic factors.25 Rich neovasculariza- Adipose Tissue as an Intrinsic and tion and sensory innervation of AT surrounding tendons may also play a role in chronic tendon Extrinsic Pain Generator pain.26 In addition, there is evidence that AT can Pain-related to AT falls into two categories: 1) contribute to the development of osteoarthri- Intrinsic: pain originating directly from/within tis via adipokines, such as leptin, visfatin and AT and 2) Extrinsic: pain related to the interac- resistin.19 Other processes, such as the loss of tion of AT with surrounding structures. Mixed the AT structural integrity, can contribute to processes are not uncommon. pain generation. This loss is observed in plantar fat pad atrophy.27 Intrinsic Pain Generation Dye et al. described pain perception of differ- ent intraarticular structures in a conscious in- Mechanisms and Biomechanics of dividual by arthroscopic probing and found the Musculoskeletal Pain Generation: infrapatellar fat pad to be both highly localized Regional Approach and sensitive compared to neighboring struc- tures.16 In an alternative study, similar noxious Lower Back and Buttock responses were induced by injecting hyperton- Episacroiliac subcutaneous lipomas, or “back ic saline (5%) into the infrapatellar fat pad.17 mice,” are subfascial fat herniations that may be encountered in patients with nonspecific Such findings underscore the rich nociceptive 4 innervation of fat pads by substance-P and low back pain. These lipomas are often bilat- calcitonin gene-related peptide nerve fibers eral and located near the sacroiliac “dimple,” and lend credibility to pain originating directly posterior iliac crest and lumbar paraspinal area. from AT.18 Moreover, AT is metabolically active (Figure 1) There appears to be a female predi- and produces proinflammatory adipokines lection. Subfascial herniation to the myofascial such as tumor necrosis factor-alpha, leptin, layer makes symptomatic lipoma difficult to vaspin, chemerin and interleukin-6.3,19,20 As an distinguish from myofascial pain syndrome. A example, pain syndromes due to inflamed fat discrete, large and painful palpable nodule fa- vors lipoma herniation rather than a myofascial pads are well described in patients with HIV. 23 These pain syndromes include retrocalcaneal trigger point. 258 Lee et al. (2020) 1:5. https://doi.org/10.36518/2689-0216.1102 Table 1. Classification of painful adipose tissue/fat pad disorders affecting lower back and lower extremity Location Common pathologies Characteristics and suggested mechanisms of pain Systemic Adipose Tissue Disorders Lipodystrophy Chronic pain with neuropathic pain most common, fol- General (congenital and lowed by arthralgia, muscle pain Common chronic periph- acquired) eral neuropathy Pain and tenderness in the bilateral lower extremities, Lipedema skin hypersensitivity, neural tissue compression within the septa surrounding fat lobules Hoffa’s fat pad with anterior (infrapatellar) knee pain and Partial Partial lipodystrophy Kager’s fat pad with posterior heel pain, anterior to the (acquired) Achilles tendon in patients with HIV infection Adiposis dolorosa Painful subcutaneous adipose tissues involving extremi- (Dercum’s disease) ties, torso and even face Adipose Tissue Pain Generation by Body Region Episacroiliac subcutaneous lipomas, “back mice”, irritating Subcutaneous painful myofascia, fascial herniation and torsion of fat pad, com- fat pad monly in the episacral region, often bilateral Can cause neuropathic pain by irritation of cluneal nerves Lower back and buttock Lipomyelomeningocele (fatty mass in conus medullaris), lipoma of the terminal filum causing tethered cord/root Spinal lipoma syndrome Spinal epidural lipomatosis (primary and secondary) with lumbosacral radiculopathy Femoral fat pad entrapment with femoroacetabular Hip and Painful fat
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