Neuropathic Pain Post Spinal Cord Injury Part 2: Systematic Review of Dorsal Root Entry Zone Procedure

Background:

Pharmacotherapy may not sufficiently reduce neuropathic pain in many individuals post spinal cord injury (SCI). The use of alternative therapies such as surgery may be effective in reducing neuropathic pain in these individuals. However, because of the invasive nature of surgery, it is important to examine the evidence for use of this treatment.

Objective:

The purpose of this study was to conduct a systematic review of published literature on the surgical treatment of neuropathic pain after SCI.

Methods:

MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles in which surgical treatment of pain after SCI was examined. Articles were restricted to the English language. Article selection was conducted by 2 independent reviewers with the following inclusion criteria: the subjects participated in a surgical intervention for neuropathic pain; at least 50% of the subjects had an SCI; at least 3 subjects had an SCI; and a definable intervention involving the dorsal root entry zone (DREZ) procedure was used to reduce pain. Data extracted included study design, study type, subject demographics, inclusion and exclusion criteria, sample size, outcome measures, and study results. Randomized controlled trials (RCTs) were assessed for quality using the Physiotherapy Evidence Database (PEDro) assessment scale. Levels of evidence were assigned to each intervention using a modified Sackett scale.

Results:

Eleven studies met the inclusion criteria. One study provided level 2 evidence, and the rest provided level 4 evidence. The DREZ procedure was shown to be more effective for segmental pain than for diffuse pain after SCI. Further, individuals with conus medullaris level injury were found to have a higher level of neuropathic pain relief than those with cervical, thoracic, or cauda equina injury.

Conclusions:

The studies demonstrated that the DREZ procedure may be effective in reducing segmental pain. Hence, DREZ may be important in treatment of neuropathic pain in individuals resistant to less invasive treatments. Because the studies lacked control conditions and examination of long-term effects, there is a need for larger trials with more stringent conditions.Key words: pain, spinal cord injury, surgical treatmentPain is a major cause of distress and disability in persons with spinal cord injury (SCI). It has been shown to lead to social isolation, unemployment, decreased function, decreased quality of life, depression, and even suicide.^1,2 More than 77% of individuals with an SCI indicated that pain interfered with one or more of their daily activities including sleep (40%), exercise (34.9%), and work (33.6%).² The International Association for the Study of Pain (IASP) defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory nervous system.”³ After an SCI, individuals often report the onset of chronic neuropathic pain caudal to the level of the lesion or at the same level within the associated spinal cord segment.⁴ Dijkers et al⁵ reported no difference in the prevalence of pain based on level or completeness.The reported incidence of neuropathic pain after SCI varies greatly among studies, but between 10% and 30% of patients with SCI experience pain severe enough to interfere with their activities of daily living^6,7 and may require surgical intervention to relieve persistent and refractory pain.^4,8 Unmanageable neuropathic pain occurs more often in individuals with conus medullaris and cauda equina lesions where damage also involves the peripheral nerve roots.⁸When pharmacological and other noninvasive treatments fail to reduce pain, surgical spinal cord stimulation and dorsal root entry zone (DREZ) ablation treatments, such as DREZ lesioning and microsurgical DREZotomy (MDT), can be considered as options for the management of refractory pain.⁹ Neurosurgical procedures to reduce neuropathic pain should be reserved for cases in which medical therapies have failed to sufficiently reduce pain.⁴ The risks associated with ablative surgeries can be significant for individuals with incomplete neurological deficits; therefore, DREZ ablation is generally only considered a treatment option when neuropathic pain is present after a complete SCI.⁸ The MDT procedure targets for ablation the nociceptive fibers in the lateral bundle of the dorsal rootlet, the deafferented neurons of the dorsal horn, and the medial portion of the Lissauer tract.^4,6 This systematic review was conducted to assess the effectiveness of DREZ ablation therapies in reducing neuropathic pain in individuals following SCI.     

Molecular identification of coxsackievirus A24 variant,isolated from an outbreak of acute hemorrhagic conjunctivitis in Singapore in 2005

Summary An outbreak of acute hemorrhagic conjunctivitis (AHC) was reported in Singapore military camps in the year 2005. A total of 103 conjunctival swab specimens were collected from military personnel diagnosed clinically with AHC. PCR testing on these conjunctival specimens revealed the presence of an enterovirus, and this was confirmed by virus isolation. Molecular typing using a partial VP1 gene confirmed a variant of coxsackievirus A24 (CA24v) as the most likely etiological agent for the outbreak. Full-length genome sequencing was carried out on 2 selected virus strains, DSO-26SIN05 and DSO-52SIN05. Sequence comparison and phylogenetic analyses of the VP4, VP1 and 3Cpro gene regions were performed, clustering the Singapore CA24v strains with viruses originating from Asia in the post-2000 era. In addition, we report evolution rates of 4.2 × 10⁻³ and 1.0 × 10⁻³ nucleotide/year, respectively, for the VP4 capsid and 3Cpro gene regions. Our result shows a focal evolutionary point around 1965–1966, suggesting that the CA24v virus has been evolving constantly since its emergence in Singapore, nearly 40 years ago.     

Presence of pro-vasopressin mRNA, neurophysin and arginine vasopressin in mouse anterior pituitary cells and the AtT-20 corticotrophic tumour cell line

Pro-vasopressin mRNA, neurophysin and arginine vasopressin (AVP) were assayed in the mouse anterior pituitary gland, in mouse anterior pituitary cells in culture and in the AtT-20 corticotrophic tumour cell line. Northern blot analysis revealed the presence of an approximately 700 base pair pro-vasopressin mRNA in anterior pituitary and AtT-20 cells. Neurophysin, identified by immunoblots, and AVP, identified by high-performance liquid chromatography and cross-reactivity with AVP antiserum, were detected in anterior pituitary cells and AtT-20 cells. Immunocytochemical staining with anti-neurophysin showed that approximately 40-45% of the dissociated anterior pituitary cells in culture and greater than 95% of the AtT-20 cells were stained. Anterior pituitary cells in culture and AtT-20 cells had a basal level of release of AVP in the 0.01-0.1 nM range. These results indicate that anterior pituitary cells and AtT-20 cells have the ability to synthesize and process pro-vasopressin to AVP and neurophysin, endogenously.