Kathryn E Lee

University of Pennsylvania, Philadelphia, PA, United States

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Publications (10)16.68 Total impact

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    Kathryn E Lee, Beth A Winkelstein
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    ABSTRACT: The facet joint is a common source of pain in both the neck and low back, and can be injured by abnormal loading of the spinal joints. Whereas a host of nociceptive changes including neuronal activation, neuropeptide expression, and inflammatory mediator responses has been reported for rat models of joint pain, no such responses have been explicitly investigated or quantified for painful mechanical injury to the facet joint. Two magnitudes of joint loading were separately imposed in a rat model of cervical facet joint distraction: Painful and nonpainful distractions. Behavioral outcomes were defined by assessing mechanical hyperalgesia in the shoulders and forepaws. Substance P (SP) mRNA and protein levels were quantified in the dorsal root ganglion (DRG) and spinal cord at days 1 and 7 following distraction. Painful distraction produced mechanical hyperalgesia that was significantly greater (P < .010) than that for a nonpainful distraction. Painful distraction significantly increased spinal SP mRNA (P = .048) and SP protein expression in the DRG (P = .013) at day 7 compared to nonpainful distraction. However, spinal SP protein for painful distraction was significantly less (P = .024) than that for nonpainful distraction at day 1. Joint distractions producing different behavioral outcomes modulate SP mRNA and protein in the DRG and spinal cord, suggesting that SP responses may be involved with different temporal responses in painful joint loading. PERSPECTIVE: SP mRNA and protein in the DRG and spinal cord are quantified at 2 time points after cervical facet joint distractions that separately do or do not produce mechanical hyperalgesia. Studies describe a role for SP to contribute to pain produced by mechanical joint loading.
    The journal of pain: official journal of the American Pain Society 05/2009; 10(4):436-45. · 3.78 Impact Factor
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    ABSTRACT: Whiplash injury can produce pain in the neck, arm, and hand, and has been associated with inflammation. However, the relationship between inflammatory responses and pain symptoms remains unknown, hindering the development of appropriate therapeutics for whiplash symptoms. Two joint loading paradigms were used separately in an established rat model of painful cervical facet joint distraction to apply: (1) gross failure, and (2) subfailure distraction of the facet capsular ligament. Behavioral outcomes were compared to determine whether more severe mechanical loading produces greater pain by measuring mechanical hyperalgesia in the shoulder and forepaws. Inflammatory mediators (glia and cytokines) were quantified in the spinal cord and dorsal root ganglion (DRG) after injury. Subfailure loading produced sustained hyperalgesia in the shoulder and forepaw that was significantly greater (p < 0.042) than sham, while an induced capsule failure produced only transient, yet significant (p < 0.021), mechanical hyperalgesia. The absence of hyperalgesia after ligament failure suggests this type of injury may interrupt nociceptive input from the capsule, which is likely necessary to produce sustained pain symptoms. Glial mRNA was significantly increased (p < 0.043) in the spinal cord after ligament failure, but remained unchanged in the DRG. Cytokine mRNA levels in the spinal cord and DRG were also significantly elevated after facet ligament failure, but not after painful subfailure loading. Findings suggest that different joint loading scenarios produced varied inflammatory responses in the CNS. These data support existing clinical reports suggesting that therapeutic interventions directed at the facet capsule may be effective in treating this painful injury.
    Journal of Neurotrauma 12/2008; 25(11):1383-93. · 4.30 Impact Factor
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    ABSTRACT: Inflammatory cytokines contribute to lumbar radiculopathy. Regulation of cytokines for transient cervical injuries, with or without longer-lasting inflammation, remains to be defined. The C7 root in the rat underwent compression (10gf), chromic gut suture exposure (chr), or their combination (10gf+chr). Ipsilateral C7 spinal cord and dorsal root ganglia (DRG) were harvested at 1 hour after injury for real-time PCR analysis of IL-1beta, IL-6, and TNF-alpha. Cytokine mRNA increased after all 3 injuries. TNF-alpha mRNA in the DRG was significantly increased over sham after 10gf+chr (P = .026). Spinal IL-1beta was significantly increased over sham after 10gf and 10gf+chr (P < .024); IL-6 was significantly increased after 10gf+chr (P < .024). In separate studies, the soluble TNF-alpha receptor was administered at injury and again at 6 hours in all injury paradigms. Allodynia was assessed and tissue samples were harvested for cytokine PCR. Allodynia significantly decreased with receptor administration for 10gf and 10gf+chr (P < .005). Treatment also significantly decreased IL-1beta and TNF-alpha mRNA in the DRG for 10gf+chr (P < .028) at day 1. Results indicate an acute, robust cytokine response in cervical nerve root injury with varying patterns, dependent on injury type, and that early increases in TNF-alpha mRNA in the DRG may drive pain-related signaling for transient cervical injuries. PERSPECTIVE: Inflammatory cytokine mRNA in the DRG and spinal cord are defined after painful cervical nerve root injury. Studies describe a role for TNF-alpha in mediating behavioral sensitivity and inflammatory cytokines in transient painful radiculopathy. Results outline an early response of inflammatory cytokine upregulation in cervical pain.
    The journal of pain: official journal of the American Pain Society 10/2008; 10(1):90-9. · 3.78 Impact Factor
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    ABSTRACT: Whiplash and its associated disorders are significant societal and health problems with half of affected patients reporting neck pain at one year after injury [1]. The cervical facet joint and its capsule have been identified in both biomechanical and clinical studies as a common site of painful injury during whiplash [2]. Also, in vivo joint distractions, which mimic the facet capsule loading reported in human cadaveric whiplash simulations, can produce behavioral hypersensitivity suggestive of chronic pain symptoms in the rat [3]. Increased laxity and decreased stiffness in the capsule are also produced after both painful joint distractions in the rat [4] and whiplash loading of the neck using cadaveric spines [5]. Together, these findings suggest that subfailure loading of the joint and its capsule produces both mechanical changes and pain. Yet, identifying the mechanical response associated with pathophysiological conditions in the capsular ligament requires an understanding of if, and how, its load-bearing microstructure is altered following painful loading.
    ASME 2008 Summer Bioengineering Conference; 06/2008
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    ABSTRACT: While studies have demonstrated the cervical facet capsule is at risk for tensile injury during whiplash, the relationship between joint loading, changes in the capsule's structure, and pain is not yet fully characterized. Complementary approaches were employed to investigate the capsule's structure-function relationship in the context of painful joint loading. Isolated C6/C7 facet joints (n=8) underwent tensile mechanical loading, and measures of structural modification were compared for two distraction magnitudes: 300 m (PV) and 700 m (SV). In a matched in vivo study, C6/C7 facet joints (n=4) were harvested after the same SV distraction and the tissue was sectioned to analyze collagen fiber organization using polarized light microscopy. Laxity following SV distraction (7.30+/-3.01%) was significantly greater (p<0.001) than that produced following PV distraction (0.99+/-0.44%). Also, SV distractions produced significantly higher maximum principal strain (p<0.001) in the capsule and resulted in significantly greater decreases in stiffness (p=0.002) when compared to PV distraction. After SV distraction in vivo, mean angular deviation of the fiber direction (16.8+/-2.6 degrees) was significantly increased (p=0.004) relative to naive samples in the lateral region of the capsule, indicating collagen fiber disorganization. These findings demonstrate that certain subfailure loading conditions are associated with altered joint mechanics and collagen fiber disorganization and imply ligament damage. Damage in the capsule has the potential to both directly modulate nerve fiber signaling and produce sustained physiologic modifications that may initiate persistent pain.
    Stapp car crash journal 10/2007; 51:169-87.
  • Kathryn E. Lee, Beth A. Winkelstein
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    ABSTRACT: Chronic neck pain following whiplash is a substantial problem, affecting as many as 42% of whiplash patients [1]. The cervical facet joint is a common candidate for producing neck pain because it sustains altered kinematics during whiplash, with tensile stretch of its capsular ligament exceeding that during normal motions [2,3]. Altered facet capsule mechanics have been documented for loading conditions below structural failure [4,5]; evidence of both decreased linear stiffness and minor ruptures of the capsule suggest ligament injury prior to failure. In vivo studies have also implicated subfailure capsule injury as a potential source of pain. Capsule nociceptive pain fiber activation and saturation [6], as well as sustained pain symptoms [7], can be produced for facet joint distraction below gross failure.
    ASME 2007 Summer Bioengineering Conference; 06/2007
  • Ling Dong, Kathryn E. Lee, Beth A. Winkelstein
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    ABSTRACT: Chronic neck pain due to whiplash injury results in 10.2 million visits to ambulatory care settings annually in the United States [1]. During the whiplash kinematic, the cervical facet joint undergoes tensile loading at a strain rate of 500–1000%/s [2,3]. In addition, distraction of the facet joint and its capsule in animal models produces both firing of pain fibers in the capsule and persistent behavioral hypersensitivity (measured by mechanical allodynia) [4,5]. In vivo studies have demonstrated a dependence of pain symptoms on the magnitude of applied joint distraction, with some distraction magnitudes not producing any changes in physiologic outcomes or pain [5]. However, in those studies, joint loading was applied quasistatically, despite the dynamic nature of whiplash. While such work provides insight into mechanisms of facet-mediated neck pain and suggests that the magnitude of joint distraction may affect pain symptoms, those studies did not incorporate the dynamic effects necessary for modeling whiplash. It remains unclear whether dynamic loading of the cervical facet joint can induce behavioral hypersensitivity, and if so, whether the degree of behavioral sensitivity depends on the distraction magnitude. This pilot study compared the effects of dynamically and quasistatically applied facet joint loading on ligament kinematics and corresponding pain symptoms.
    ASME 2007 Summer Bioengineering Conference; 06/2007
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    ABSTRACT: Clinical, epidemiological, and biomechanical studies suggest the involvement of the cervical facet joint in neck pain. Mechanical studies have suggested the facet capsular ligament to be at risk for subfailure tensile injury during whiplash kinematics of the neck. Ligament mechanical properties can be altered by subfailure injury and such loading can induce cellular damage. However, at present, there is no clear understanding of the physiologic context of subfailure facet capsular ligament injury and mechanical implications for whiplash-related pain. Therefore, this study aimed to define a relationship between mechanical properties at failure and a subfailure condition associated with pain for tension in the rat cervical facet capsular ligament. Tensile failure studies of the C6/C7 rat cervical facet capsular ligament were performed using a customized vertebral distraction device. Force and displacement at failure were measured and stiffness and energy to failure were calculated. Vertebral motions and ligament deformations were tracked and maximum principal strains and their directions were calculated. Mean tensile force at failure (2.96 +/- 0.69 N) was significantly greater (p < 0.005) than force at subfailure (1.17 +/- 0.48 N). Mean ligament stiffness to failure was 0.75 +/- 0.27 N/mm. Maximum principal strain at failure (41.3 +/- 20.0%) was significantly higher (p = 0.003) than the corresponding subfailure value (23.1 +/- 9.3%). This study determined that failure and a subfailure painful condition were significantly different in ligament mechanics and findings provide preliminary insight into the relationship between mechanics and pain physiology for this ligament. Together with existing studies, these findings offer additional considerations for defining mechanical thresholds for painful injuries.
    Journal of Biomechanics 01/2006; 39(7):1256-64. · 2.72 Impact Factor
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    ABSTRACT: While extensive research points to mechanical injury of the cervical facet joint as a mechanism of whiplash injury, findings remain speculative regarding its potential for causing pain. The purpose of this study was to examine the relationship between facet joint distraction, capsular ligament strain, cellular nociceptive responses, and pain. A novel rat model of in vivo facet joint injury was used to impose C6/C7 joint distraction in separate studies of subcatastrophic and physiologic vertebral distraction, as well as sham procedures. A common clinical measure of behavioral hypersensitivity (allodynia) was measured for 14 days after injury, as quantification of resulting pain symptoms. Also, on day 14, spinal activation of microglia and astrocytes was quantified to examine the potential role of glial activation as a physiologic mechanism of facet-mediated painful injury. Vertebral distractions of 0.90+/-0.53 mm across the rat facet joint reliably produced symptoms of persistent pain. Allodynia results showed immediate and sustained behavioral sensitivity following subcatastrophic vertebral distractions; pain symptoms were significantly greater (p<0.008) than those for other injury groups. Further, spinal astrocytic activation was also greater (p=0.049) for subcatastrophic injuries compared to lower distraction magnitudes. The mean maximum principal strain in the capsular ligament for joint distractions of 0.57+/-0.11 mm was 27.7+/-11.9%. Findings suggest that facet capsule strains comparable to those previously reported for whiplash kinematics and subcatastrophic failures of this ligament have the potential to produce pain symptoms and alter one element of nociception. Results further suggest that a mechanical threshold likely exists for painful joint distraction, providing behavioral and physiologic evidence of the cervical facet joint's mechanical injury as a source of neck pain.
    Stapp car crash journal 12/2004; 48:373-95.
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    ABSTRACT: Clinical, epidemiological, and biomechanical studies suggest involvement of cervical facet joint injuries in neck pain. While bony motions can cause injurious tensile facet joint loading, it remains speculative whether such injuries initiate pain. There is currently a paucity of data explicitly investigating the relationship between facet mechanics and pain physiology. A rodent model of tensile facet joint injury has been developed using a customized loading device to apply two separate tensile deformations (low, high; n = 5 each) across the C6/C7 joint, or sham (n = 6) with device attachment only. Microforceps were rigidly coupled to the vertebrae for distraction and joint motions tracked in vivo. Forepaw mechanical allodynia was measured postoperatively for 7 days as an indicator of behavioral sensitivity. Joint strains for high (33.6 +/- 3.1%) were significantly elevated (P < 0.005) over low (11.1 +/- 2.3%). Digitization errors (0.17 +/- 0.20%) in locating bony markers were small compared to measured strains. Allodynia was significantly elevated for high over low and sham for all postoperative days. However, allodynia for low injury was not different than sham. A greater than three-fold increase in total allodynia resulted for high compared to low, corresponding to the three-fold difference in injury strain. Findings demonstrate tensile facet joint loading produces behavioral sensitivity that varies in magnitude according to injury severity. These results suggest that a facet joint tensile strain threshold may exist above which pain symptoms result. Continued investigation into the relationship between injury mechanics and nociceptive physiology will strengthen insight into painful facet injury mechanisms.
    Journal of Neuroscience Methods 09/2004; 137(2):151-9. · 2.11 Impact Factor