Gatchel RJ, Mayer TG, Chou R. What does/should the minimum clinically important difference measure? Clin. J. Pain 28, 387–397 (2012).
The authors argue that the minimum clinically important difference (MCID) has failed to achieve its purported goal of providing a standardized outcome measure. In part, this is due to the use of a wide range of criteria for determining outcomes, from the way the patient feels to quantifying what the patient actually does or does not do. The MCID was initially proposed as a much more relevant measure than reporting statistical significance of a variety of measures; it is now widely recognized that statistical significance is not a proxy for clinical significance. However, MCID for measures that reflect ‘feeling better‘ many not be relevant to MCID for ‘doing better‘ measures. As the authors point out, most of the studies that allege that fusion operations on the lumbar spine are beneficial make use of ‘feeling better‘ measures and not objective ‘doing better‘ criteria. The authors propose that a biopsychosocial model of human behavior be utilized and that outcomes be captured in three domains:
Self-report (‘feeling better‘)
Functional performances (‘doing better‘)
Objective external socioeconomic outcomes
They also argue for the utilization of both distribution-based analyses of change and anchor-based analyses as each one of these by itself can lead to inadequate interpretations of the data. Utilizing the three domains in every report of outcomes from a procedure or treatment program will greatly enhance our knowledge of what works and what does not.
– Written by John D Loeser
Millecamps M, Tajerian M, Naso L, Sage EH, Stone LS. Lumbar intervertebral disc degeneration associated with axial and radiating low back pain in ageing SPARC-null mice. Pain 153, 1167–1179 (2012).
This article describes a lovely translational study of some of the relevant factors in chronic low back pain. SPARC is a matricellular protein that is important in the response to injury and the subsequent tissue remodeling. Mice who are SPARC-null exhibit accelerated age-dependent disc degeneration as well as behavioral signs suggestive of chronic back pain. Disc degeneration and increasing age in humans are also associated with a decrease in intervertebral SPARC.
SPARC-null mice develop degenerative disc changes earlier and more severely than wild-type mice. Not only are there correlative x-ray changes typical of disc degeneration but there are also histological changes similar to those seen in humans. These mice manifest a variety of behavioral changes that imply pain with axial movement and pain referred to the lower extremity and foot. The sensory changes were not found in the upper lip, suggesting that they were not due to a systemic effect of SPARC-null condition. The restriction in axial movement and leg pain were ameliorated by morphine.
This study has many strengths. It was longitudinal and lasted for 72 weeks, making it more akin to chronic pain in humans. The motor impairment was correlated with the development of disc degeneration. Behavioral changes were observed; raising the possibility that the SPARC-null mouse could be used as a model for many of the phenomena of low back pain in humans. There are far too few models of chronic pain in experimental animals, especially chronic low back pain. Unlike most of the neuropathic pain models, the low back pain in SPARC-null mice is not transient. I believe that this study will lead to many more utilizing a variety of knockout mice; hopefully, we will begin to unravel the puzzle of low back pain.
– Written by John D Loeser
Campbell CM, Kipnes MS, Stouch BC et al. Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy. Pain 153(9), 1815–1823 (2012).
Painful diabetic polyneuropathy is a common complication to diabetes and patients may not obtain sufficient pain relief with currently recommended drugs. In this randomized controlled trial, patients were classified according to their response to a topical capsaicin application. The study demonstrated that topical treatment with clonidine is less likely to have an effect if the treated skin is profoundly denervated. The study is an important step for individualized treatment approaches and suggests that screening for cutaneous nociceptor function may help distinguish candidates for topical therapy for neuropathic pain.
– Written by Nanna B Finnerup
Bráz JM, Sharif-Naeini R, Vogt D et al. Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain. Neuron 74(4), 663–75 (2012).
Loss of inhibitory GABAergic signaling in the spinal cord is thought to be one mechanism contributing to chronic peripheral neuropathic pain. In this study, transplantation of precursor cells of cortical GABAergic neurons into the spinal dorsal horn reversed persistent neuropathic pain-like responses in mice. The authors showed how the transplanted neurons differentiate into GABAergic neurons and establish synaptic connections with primary nociceptors as well as secondary dorsal horn neurons and functionally respond to peripheral stimulation. The transplantation reversed signs of mechanical allodynia and although further studies will be required, this paradigm may represent a new potential therapeutic intervention.
– Written by Nanna B Finnerup
Bowman RG, Caraway D, Bentley I. Comparison of a novel fixation device with standard suturing methods for spinal cord stimulators. Neuromodulation doi:10.1111/j.1525–1403.2012.00480x (2012) (Epub ahead of print).
Investigators undertook laboratory testing of three different models to assess the strength of a semiautomated device (fiXate) designed to suture spinal cord stimulator anchors to fascia to prevent lead migration after implantation. In each model, both hand-tied and fiXate-placed sutures were placed under a force gauge to determine the necessary force to pull the suture through the fascia. Six samples in each of three models were tested:
A perpendicular pull from the fascia of a caprine spine
An axial pull from the fascia of a caprine spine
An axial pull from Mylar film
Regarding a perpendicular pull in a caprine spine, mean failure loads were 8.95 lb for a standard suture, and 15.93 lb for the device-placed suture. When an axial pull was applied in a caprine spine to a standard suture, the failure load was 6.79 lb as opposed to 12.31 lb for the device-placed suture. For an axial pull in Mylar film, the failure load was 10.87 lb for the standard suture and 19.54 lb for the device-placed suture. A limitation of the study is that the investigators applied force to the suture rather than to a lead placed through an anchor fixed with a given suturing technique. Such a study in the future might have more relevance to the actual dynamics of lead migration for implanted spinal cord stimulator leads.
– Written by Michael Erdek
Yaksh TL, de Kater A, Dean R et al. Pharmacokinetic analysis of ziconotide (SNX-111), an intrathecal N-type calcium channel blocking analgesic, delivered by bolus and infusion in the dog. Neuromodulation doi:10.1111/j.1525–1403.2012.00479x (2012) (Epub ahead of print).
Investigators implanted five male beagle dogs with intrathecal (IT) lumbar injection and sampling catheters to assess the kinetics of intrathecal ziconotide administered intrathecally by bolus and by continuous infusion. Each dog received four different treatments:
IT bolus ziconotide (10 µg)
IT ziconotide infusion for 48 h (1 µg/100 µl/h)
IT ziconotide infusion for 48 h (5 µg/100 µl/h)
Intravenous injection of ziconotide (0.1 mg/kg)
Peak cerebrospinal fluid concentration of bolus and IT infusion ziconotide was appreciated at 0.14 and 8 h, respectively. IT infusion elimination half-life was 2.47 h for the drug at the end of the 48 h infusion. IT bolus ziconotide injection resulted in trembling, decreased arousal, no change in body temperature, modest decrease in blood pressure, mild increase in heart rate, but no effect on nociception as measured by skin twitch response. After beginning the 1 µg/h IT infusion, dogs exhibited trembling, ataxia and decreased arousal that tended to increase after the infusion was increased to 5 µg/h. This group manifested a modest increase in body temperature and no change in blood pressure, but did demonstrate tachycardia. Importantly, the IT infusion-treated animals showed no effect of antinociception at 8 h, but complete abolition of skin twitch response at 24 h of infusion.
– Written by Michael Erdek
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.