Painful Distraction Research Articles

Targeted Partial Arthroscopic Trapeziectomy and Distraction: Surgical Technique

Basal joint osteoarthritis is a real public health problem, yet there is no consensus on its treatment. Although total trapeziectomy, as well as arthroplasty, provides long-lasting efficacy, it does not seem to be adapted to a young population with complications that are often very difficult to manage. In the era of minimally invasive surgery, there is a real interest in finding conservative therapeutic alternatives for young subjects that allow them to “pass a painful milestone” and, thus, postpone the least conservative interventions. This article details the surgical technique of an arthroscopic and conservative technique: The Targeted Partial Arthroscopic Trapeziectomy and Distraction based on two goals: targeted resection of painful arthritic lesions and distraction of the joint to restore ligament tension and hopefully regrow fibrocartilage on resected lesions.

3.54 A Painful Distraction? Nonsuicidal Self-Injury in Pediatric Inpatients and Its Relationship With Caregiver Stress

3.54 A Painful Distraction? Nonsuicidal Self-Injury in Pediatric Inpatients and Its Relationship With Caregiver Stress

Magnetically controlled growing rod in early onset scoliosis: a 30-case multicenter study

Preliminary results of magnetically controlled growing rods (MCGR) are encouraging. However, only short case series of MCGR for the treatment of early onset scoliosis (EOS) have been reported. Our aim was to evaluate its effectiveness and complications. We report a 30-case retrospective, consecutive, multicenter series of MCGR. Effectiveness was judged upon: deformity correction and difficulties to achieve desired distraction. Secondary endpoints included complications and revision surgeries. Median age at surgery was 9.1years (5-13). Mean follow-up was 18.4months (12-33.9). Mean Cobb angle was 66° preoperatively and 44° at latest follow-up. MCGR has avoided an average of 2.03 scheduled surgical procedures per patient compared to traditional growing rod (GR). The intended total length gain was 40.1mm per patient (5-140) and the total measured length gain was 21.9mm (45.5% discrepancy). There were 24 complications: 7 proximal pull-outs of the hooks, 3 rod breakages, 6 failures of the lengthening of which 4 complete blockages and 2 complete blockages followed by backtracking, 1 proximal junctional kyphosis, 1 wound dehiscence, 1 superficial infection, 1 deep infection requiring implant removal, 1 pulmonary embolism, 1 pulmonary insufficiency, 1 secondary lumbar scoliosis, and 1 painful outpatient distraction. Eight patients had a gradual loss of effectiveness of distractions. There were 13 revision surgeries in 9 patients. MCGR provides satisfactory deformity correction and avoids repeated surgical procedures for lengthening. However, it has substantial complication rate. Although less frequent than in GR, the law of diminishing returns also applies to MCGR.

Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity

The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain.

Gabapentin Alleviates Facet-Mediated Pain in the Rat Through Reduced Neuronal Hyperexcitability and Astrocytic Activation in the Spinal Cord

Although joint pain is common, its mechanisms remain undefined, with little known about the spinal neuronal responses that contribute to this type of pain. Afferent activity and sustained spinal neuronal hyperexcitability correlate to facet joint loading and the extent of behavioral sensitivity induced after painful facet injury, suggesting that spinal neuronal plasticity is induced in association with facet-mediated pain. This study used a rat model of painful C6-C7 facet joint stretch, together with intrathecal administration of gabapentin, to investigate the effects of one aspect of spinal neuronal function on joint pain. Gabapentin or saline vehicle was given via lumbar puncture prior to and at 1 day after painful joint distraction. Mechanical hyperalgesia was measured in the forepaw for 7 days. Extracellular recordings of neuronal activity and astrocytic and microglial activation in the cervical spinal cord were evaluated at day 7. Gabapentin significantly (P = .0001) attenuated mechanical hyperalgesia, and the frequency of evoked neuronal firing also significantly decreased (P < .047) with gabapentin treatment. Gabapentin also decreased (P < .04) spinal glial fibrillary acidic protein expression. Although spinal Iba1 expression was doubled over sham, gabapentin did not reduce it. Facet joint–mediated pain appears to be sustained through spinal neuronal modifications that are also associated with astrocytic activation. PerspectiveIntrathecal gabapentin treatment was used to investigate behavioral, neuronal, and glial response in a rat model of painful C6-C7 facet joint stretch. Gabapentin attenuated mechanical hyperalgesia, reduced evoked neuronal firing, and decreased spinal astrocytic activation. This study supports that facet joint pain is sustained through spinal neuronal and astrocytic activation.

Brain-derived neurotrophic factor is upregulated in the cervical dorsal root ganglia and spinal cord and contributes to the maintenance of pain from facet joint injury in the rat

The facet joint is commonly associated with neck and low back pain and is susceptible to loading-induced injury. Although tensile loading of the cervical facet joint has been associated with inflammation and neuronal hyperexcitability, the mechanisms of joint loading-induced pain remain unknown. Altered brain-derived neurotrophic factor (BDNF) levels are associated with a host of painful conditions, but the role of BDNF in loading-induced joint pain remains undefined. Separate groups of rats underwent a painful cervical facet joint distraction or a sham procedure. Bilateral forepaw mechanical hypersensitivity was assessed and BDNF mRNA and protein levels were quantified in the dorsal root ganglion (DRG) and spinal cord at days 1 and 7. Facet joint distraction induced significant (P < 0.001) mechanical hypersensitivity at both time points. Painful joint distraction did not alter BDNF mRNA in the DRG compared with sham levels but did significantly increase (P < 0.016) BDNF protein expression over sham in the DRG at day 7. Painful distraction also significantly increased BDNF mRNA (P = 0.031) and protein expression (P = 0.047) over sham responses in the spinal cord at day 7. In a separate study, intrathecal administration of the BDNF-sequestering molecule trkB-Fc on day 5 after injury partially attenuated behavioral sensitivity after joint distraction and reduced pERK in the spinal cord at day 7 (P < 0.045). Changes in BDNF after painful facet joint injury and the effect of spinal BDNF sequestration in partially reducing pain suggest that BDNF signaling contributes to the maintenance of loading-induced facet pain but that additional cellular responses are also likely involved.

Ketorolac reduces spinal astrocytic activation and PAR1 expression associated with attenuation of pain after facet joint injury.

Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain.

An Anatomical and Immunohistochemical Characterization of Afferents Innervating the C6–C7 Facet Joint After Painful Joint Loading in the Rat

This study used retrograde neuronal tracing and immunohistochemistry to identify neurons innervating the C6-C7 facet joint and those expressing calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG) of rats after painful cervical facet joint injury. The objective of this study was to characterize the innervation of the C6-C7 facet joint after painful joint injury in the rat. The cervical facet joint is a source of neck pain, and its loading can initiate persistent pain. CGRP is a nociceptive neurotransmitter; peptidergic afferents have been identified in the facet joint's capsule. Although studies suggest that facet joint injury alters CGRP expression in joint afferents, the distribution of neurons innervating the C6-C7 facet joint and their expression of CGRP after a painful joint injury have not been investigated. Holtzman rats (Harlan Sprague-Dawley, Indianapolis, IN) received an intra-articular injection of cholera toxin subunit B in the C6-C7 facet joints. After injection, subgroups underwent either a painful joint distraction or sham procedure. Mechanical sensitivity was assessed, and immunohistochemical techniques were used to quantify CGRP expression and cholera toxin subunit B labeling in the C5-C8 DRGs. Facet joint distraction-induced (P ≤ 0.0002) hypersensitivity. Neurons labeled by the joint injection were identified in the C5-C8 DRGs. Significantly, more (P ≤ 0.0001) cholera toxin subunit B-positive neurons were identified in the C7 DRG than any other level. At C7, 54.4% ± 15.3% of those neurons were also CGRP-positive, whereas only 41.5% ± 5.4% of all neurons were CGRP-positive; this difference was significant (P = 0.0084). The greatest number of afferents from the C6-C7 facet joint has cell bodies in the C7 DRG, implicating this level as the most relevant for pain from this joint. In addition, peptidergic afferents seem to have an important role in facet joint-mediated pain.

The Prostaglandin E2 Receptor, EP2, Is Upregulated in the Dorsal Root Ganglion After Painful Cervical Facet Joint Injury in the Rat

This study implemented immunohistochemistry to assay prostaglandin E2 (PGE2) receptor EP2 expression in the dorsal root ganglion (DRG) of rats after painful cervical facet joint injury. To identify if inflammatory cascades are induced in association with cervical facet joint distraction-induced pain by investigating the time course of EP2 expression in the DRG. The cervical facet joint is a common source of neck pain, and nonphysiological stretch of the facet capsular ligament can initiate pain from the facet joint via mechanical injury. PGE2 levels are elevated in painful inflamed and arthritic joints, and PGE2 sensitizes joint afferents to mechanical stimulation. Although in vitro studies suggest that the EP2 receptor subtype contributes to painful joint disease, the EP2 response has not been investigated for any association with painful mechanical joint injury. Separate groups of male Holtzman rats underwent either a painful cervical facet joint distraction injury or sham procedure. Bilateral forepaw mechanical allodynia was assessed, and immunohistochemical techniques were used to quantify EP2 expression in the DRG at days 1 and 7. Facet joint distraction induced mechanical allodynia that was significant (P < 0.024) at all time points. Painful joint injury also significantly elevated total EP2 expression in the DRG at day 1 (P = 0.009), which was maintained at day 7 (P < 0.001). Neuronal expression of EP2 in the DRG was only increased over sham levels at day 1 (P = 0.013). Painful cervical facet joint distraction induces an immediate and sustained increase of EP2 expression in the DRG, implicating peripheral inflammation in the initiation and maintenance of facet joint pain. The transient increase in neuronal EP2 suggests, as in other painful joint conditions, that after joint injury nonneuronal cells may migrate to the DRG, some of which likely express EP2.

Whiplash-like facet joint loading initiates glutamatergic responses in the DRG and spinal cord associated with behavioral hypersensitivity

The cervical facet joint and its capsule are a common source of neck pain from whiplash. Mechanical hyperalgesia elicited by painful facet joint distraction is associated with spinal neuronal hyperexcitability that can be induced by transmitter/receptor systems that potentiate the synaptic activation of neurons. This study investigated the temporal response of a glutamate receptor and transporters in the dorsal root ganglia (DRG) and spinal cord. Bilateral C6/C7 facet joint distractions were imposed in the rat either to produce behavioral sensitivity or without inducing any sensitivity. Neuronal metabotropic glutamate receptor-5 (mGluR5) and protein kinase C-epsilon (PKCε) expression in the DRG and spinal cord were evaluated on days 1 and 7. Spinal expression of a glutamate transporter, excitatory amino acid carrier 1 (EAAC1), was also quantified at both time points. Painful distraction produced immediate behavioral hypersensitivity that was sustained for 7days. Increased expression of mGluR5 and PKCε in the DRG was not evident until day 7 and only following painful distraction; this increase was observed in small-diameter neurons. Only painful facet joint distraction produced a significant increase (p<0.001) in neuronal mGluR5 over time, and this increase also was significantly elevated (p≤0.05) over responses in the other groups at day 7. However, there were no differences in spinal PKCε expression on either day or between groups. Spinal EAAC1 expression was significantly increased (p<0.03) only in the nonpainful groups on day 7. Results from this study suggest that spinal glutamatergic plasticity is selectively modulated in association with facet-mediated pain.

Activating transcription factor 4, a mediator of the integrated stress response, is increased in the dorsal root ganglia following painful facet joint distraction

Chronic neck pain is one of the most common musculoskeletal disorders in the US. Although biomechanical and clinical studies have implicated the facet joint as a primary source of neck pain, specific cellular mechanisms still remain speculative. The purpose of this study was to investigate whether a mediator (activating transcription factor; 4ATF4) of the integrated stress response (ISR) is involved in facet-mediated pain. Holtzman rats underwent C6/C7 facet joint loading that produces either painful (n=16) or nonpainful (n=8) responses. A sham group (n=9) was also included as surgical controls. Behavioral sensitivity was measured and the C6 dorsal root ganglia (DRGs) were harvested on day 7 to evaluate the total and neuronal ATF4 expression. In separate groups, an intra-articular ketorolac injection was administered either immediately (D0 ketorolac) or 1 day (D1 ketorolac) after painful facet joint loading. Allodynia was measured at days 1 and 7 after injury to assess the effects on behavioral responses. ATF4 and BiP (an indicator of ISR activation) were separately quantified at day 7. Facet joint loading sufficient to elicit behavioral hypersensitivity produced a threefold increase in total and neuronal ATF4 expression in the DRG. After ketorolac treatment at the time of injury, ATF4 expression was significantly (P<0.01) reduced despite not producing any attenuation of behavioral responses. Interestingly, ketorolac treatment at day 1 significantly (P<0.001) alleviated behavioral sensitivity at day 7, but did not modify ATF4 expression. BiP expression was unchanged after either intervention time. Results suggest that ATF4-dependent activation of the ISR does not directly contribute to persistent pain, but it may sensitize neurons responsible for pain initiation. These behavioral and immunohistochemical findings imply that facet-mediated pain may be sustained through other pathways of the ISR.

Simulated Whiplash Modulates Expression of the Glutamatergic System in the Spinal Cord Suggesting Spinal Plasticity Is Associated with Painful Dynamic Cervical Facet Loading

The cervical facet joint and its capsule have been reported to be injured during whiplash scenarios and are a common source of chronic neck pain from whiplash. Both the metabotropic glutamate receptor 5 (mGluR5) and the excitatory amino acid carrier 1 (EAAC1) have pivotal roles in chronic pain. In this study, spinal mGluR5 and EAAC1 were quantified following painful facet joint distraction in a rat model of facet-mediated painful loading and were evaluated for their correlation with the severity of capsule loading. Rats underwent either a dynamic C6/C7 joint distraction simulating loading experienced during whiplash (distraction; n = 12) or no distraction (sham; n = 6) to serve as control. The severity of capsular loading was quantified using strain metrics, and mechanical allodynia was assessed after surgery. Spinal cord tissue was harvested at day 7 and the expression of mGluR5 and EAAC1 were quantified using Western blot analysis. Mechanical allodynia following distraction was significantly (p < 0.001) higher than sham. Spinal expression of mGluR5 was also significantly (p < 0.05) greater following distraction relative to sham. However, spinal EAAC1 was significantly (p = 0.0003) reduced compared to sham. Further, spinal mGluR5 expression was significantly positively correlated to capsule strain (p < 0.02) and mechanical allodynia (p < 0.02). Spinal EAAC1 expression was significantly negatively related to one of the strain metrics (p < 0.003) and mechanical allodynia at day 7 (p = 0.03). These results suggest that the spinal glutamatergic system may potentiate the persistent behavioral hypersensitivity that is produced following dynamic whiplash-like joint loading; chronic whiplash pain may be alleviated by blocking mGluR5 expression and/or enhancing glutamate transport through the neuronal transporter EAAC1.

Joint Distraction Magnitude Is Associated With Different Behavioral Outcomes and Substance P Levels for Cervical Facet Joint Loading in the Rat

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. 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.

Capsular Ligament Involvement in the Development of Mechanical Hyperalgesia after Facet Joint Loading: Behavioral and Inflammatory Outcomes in a Rodent Model of Pain

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.

An Intact Facet Capsular Ligament Modulates Behavioral Sensitivity and Spinal Glial Activation Produced by Cervical Facet Joint Tension

In vivo experiments using a rat model of painful facet joint distraction. To determine whether tension of the facet capsular ligament is requisite for producing pain for joint loading and to define effects on spinal glial activation. Cervical facet joint loading may initiate pain for certain conditions. While facet capsule tension has been proposed as requisite for pain, this hypothesis has not been tested. Using an established rat model of painful C6-C7 distraction, tension was applied after transection of the left facet capsule; the right capsule remained intact. Each rat (n = 8) received the same distraction simultaneously applied across both the intact and cut capsules. Sham procedures were performed on separate rats (n = 4) with no joint distraction. Bilateral forepaw mechanical allodynia was measured as a pain outcome. Cervical spinal cord tissue (C7) was harvested on day 7 to detect glial reactivity using immunohistochemistry. Distraction mechanics were consistent with conditions eliciting persistent behavioral hypersensitivity. Allodynia was produced for an intact capsule and was significantly elevated over both the cut capsule (P < 0.004) and sham (P < 0.002). Transecting the capsule before distraction did not produce elevated allodynia, except on day 7. Spinal astrocytic reactivity paralleled allodynia; glial fibrillary acidic protein expression for an intact capsule was significantly greater than the cut and sham responses (P < 0.04), with no difference observed between the cut and sham spinal astrocytic reactivity. Spinal microglial activation did not differ between groups. Results suggest ligament tension may be required to produce pain from facet joint loading. Further studies of other cellular responses are needed to define the mechanisms of painful facet joint injury.

Comparison of hypnosis and distraction in severely ill children undergoing painful medical procedures.

An ethnically diverse sample of high and low hypnotizable children (N = 27) suffering from cancer or blood disorders and their parents were trained to use both distraction and hypnosis to reduce pain and anxiety. Measures of pain and anxiety were obtained from the children and their parents. Independent raters also judged participants' video-taped distress responses. Data were collected during painful medical procedures, for baseline, distraction, and hypnosis conditions. Supporting E. R. Hilgard's (1977, 1992) neodissociation theory, hypnotizable children showed significantly lower pain, anxiety, and distress scores in response to hypnosis in contrast to the low hypnotizable children. Distraction produced significant positive effects for observer-rated distress scores for the low hypnotizable children.

Elevation of pain threshold by vaginal stimulation in women

In 2 studies with 10 women each, vaginal self-stimulation significantly increased the threshold to detect and tolerate painful finger compression, but did not significantly affect the threshold to detect innocuous tactile stimulation. The vaginal self-stimulation was applied with a specially designed pressure transducer assembly to produce a report of pressure or pleasure. In the first study, 6 of the women perceived the vaginal stimulation as producing pleasure. During that condition, the pain tolerance threshold increased significantly by 36.8% and the pain detection threshold increased significantly by 53%. A second study utilized other types of stimuli. Vaginal self-stimulation perceived as pressure significantly increased the pain tolerance threshold by 40.3% and the pain detection threshold by 47.4%. In the second study, when the vaginal stimulation was self-applied in a manner that produced orgasm, the pain tolerance threshold and pain detection threshold increased significantly by 74.6% and 106.7% respectively, while the tactile threshold remained unaffected. A variety of control conditions, including various types of distraction, did not significantly elevate pain or tactile thresholds. We conclude that in women, vaginal self-stimulation decreases pain sensitivity, but does not affect tactile sensitivity. This effect is apparently not due to painful or non-painful distraction.