The Nervous System by Dr. Cox

In my 55 years as a chiropractic doctor I have seen great controversy but none greater than that of the role of the nervous system in human disease origin. Nerve compression today is being studied and its conclusions regenerate the early chiropractic concepts of human disease. Let’s look at the following two papers published and in this pearl.

James M. Cox, DC, DACBR, FACO(H)

INTERVERTEBRAL DISC GENERATED PAIN DUE TO SYMPATHETIC NERVE SUPPLY

INTERVERTEBRAL DISC DISEASES (IVDDS) AFFECTING PATHOLOGICAL CHANGES LEADING TO DISC HERNIATION, PROLAPSE AND DEGENERATION AS WELL AS DISCOGENIC PAIN IS STUDIED FOR SYMPATHETIC NERVE INVOLVED IN PAIN SIGNALLING IN IVDD PATIENTS. PIGS WERE GIVEN AN INJECTION OF THE OMINIPAQUE CONTRAST AGENT AND FAST BLUE (FB) RETROGRADE TRACER INTO THE L4-L5 INTERVERTEBRAL DISC AND EUTHANIZED AT 2, 1, AND 3 MONTHS POST INJECTION. FOLLOWING EUTHANASIA, BILATERAL SYMPATHETIC CHAIN GANGLIA (SCHG) TH13 TO C1 WERE COLLECTED. THE PRESENCE, DISTRIBUTION AND NEUROCHEMICAL CHARACTERISTICS OF RETROGRADELY LABELLED SCHG NEURONS WERE EXAMINED. THE MAJORITY (88.8%) OF ALL FB+ CELLS WERE FOUND IN THE L3-L5 SCHG. MOST FB+ NEURONS STAINED FOR DOPAMINE BETA HYDROXYLASE (DBH); ONE-THIRD TO ONE-QUARTER STAINED FOR SOMATOSTATIN (SOM), NEUROPEPTIDE Y (NPY) OR LEU-ENKEPHALIN (LENK); AND ONLY A FEW STAINED FOR GALANIN (GAL). COMPARED WITH THE CONTROL, THE GREATEST DECLINE IN NEUROCHEMICAL IMMUNOSTAINING WAS OBSERVED 2 WEEKS POST INJECTION, AND THE LOWEST DECLINE WAS NOTICED 1 MONTH POST INJECTION. OUR STUDY, FOR THE FIRST TIME, PROVIDES INSIGHT INTO THE COMPLEX PATTERNS OF INTERVERTEBRAL DISC SYMPATHETIC INNERVATION AND SUGGESTS THAT THE BEST TIME FOR NEUROCHEMICAL BALANCE RESTORATION THERAPY WOULD BE 1 MONTH POST-INJURY, WHEN THE NEURONAL CONCENTRATION OF ALL STUDIED SUBSTANCES IS CLOSE TO THE INITIAL PHYSIOLOGICAL LEVEL, THUS PROVIDING FAVOURABLE CONDITIONS FOR SUCCESSFUL RECOVERY.

Barczewska M, Juranek J, Wojtkiewicz J. Origins and Neurochemical Characteristics of Porcine Intervertebral Disc Sympathetic Innervation: a Preliminary Report. J Mol Neurosci. 2017 Jul 31. doi: 10.1007/s12031-017-0956-3. [Epub ahead of print]

Intervertebral disc diseases (IVDDs) form a group of a vertebral column disorders affecting a large number of people worldwide. It is estimated that approximately 30% of individuals at the age of 35 and approximately 90% of individuals at the age of 60 and above will have some form of disc-affecting pathological changes leading to disc herniation, prolapse and degeneration as well as discogenic pain. Here, we aimed to establish the origins and neurochemical characteristics of porcine intervertebral disc sympathetic innervation involved in pain signalling in IVDD patients. Pigs were given an injection of the Ominipaque contrast agent and Fast Blue (FB) retrograde tracer into the L4-L5 intervertebral disc and euthanized at 2, 1, and 3 months post injection. Following euthanasia, bilateral sympathetic chain ganglia (SChG) Th13 to C1 were collected. The presence, distribution and neurochemical characteristics of retrogradely labelled SChG neurons were examined. The majority (88.8%) of all FB+ cells were found in the L3-L5 SChG. Most FB+ neurons stained for dopamine beta hydroxylase (DBH); one-third to one-quarter stained for somatostatin (SOM), neuropeptide Y (NPY) or leu-enkephalin (LENK); and only a few stained for galanin (GAL). Compared with the control, the greatest decline in neurochemical immunostaining was observed 2 weeks post injection, and the lowest decline was noticed 1 month post injection. Our study, for the first time, provides insight into the complex patterns of intervertebral disc sympathetic innervation and suggests that the best time for neurochemical balance restoration therapy would be 1 month post-injury, when the neuronal concentration of all studied substances is close to the initial physiological level, thus providing favourable conditions for successful recovery.

CHRONIC CONSTRICTION INJURY OF SCIATIC NERVE DORSAL HORNS CHANGES CIRCULAR RNA (CIRCRNA)EXPRESSION IN RAT SPINAL DORSAL HORN TO CAUSE NEUROPATHIC PAIN AT THE LUMBAR ENLARGEMENT SEGMENTS (L3-L5). CIRCRNA MICROARRAYS SHOWED THAT 469 CIRCRNAS WERE DIFFERENTIALLY EXPRESSED BETWEEN CCI AND SHAM-OPERATED RATS. THREE OF THEM (CIRCRNA_013779, CIRCRNA_008008, AND CIRCRNA_003724) OVEREXPRESSED >10 TIMES AFTER CCI INSULT. CCI RESULTED IN A COMPREHENSIVE EXPRESSION PROFILE OF CIRCRNAS IN THE SPINAL DORSAL HORN IN RATS. CIRCRNAS IN THE DORSAL HORN COULD BE HELPFUL TO REVEAL MOLECULAR MECHANISMS OF NEUROPATHIC PAIN.

Cao S, Deng W, Li Y, Qin B, Zhang L, Yu S, Xie P, Xiao Z, Yu T. Chronic constriction injury of sciatic nerve changes circular RNA expression in rat spinal dorsal horn. J Pain Res. 2017 Jul 17;10:1687-1696. doi: 10.2147/JPR.S139592. eCollection 2017.

BACKGROUND: Mechanisms of neuropathic pain are still largely unknown. Molecular changes in spinal dorsal horn may contribute to the initiation and development of neuropathic pain. Circular RNAs (circRNAs) have been identified as microRNA sponges and involved in various biological processes, but whether their expression profile changes in neuropathic pain condition is not reported.

METHODS: To test whether neuropathic pain influences circRNA expression, we developed a sciatic chronic constriction injury (CCI) model in rats. The CCI ipsilateral spinal dorsal horns of lumbar enlargement segments (L3-L5) were collected, and the total RNA was extracted and subjected to Arraystar Rat circRNA Microarray. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the circRNA expression profile. To estimate functions of differential circRNAs, bioinformatics analyses including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes Pathway analyses were performed for the top 100 circRNAs and circRNA-microRNA networks were constructed for the top 10 circRNAs.

RESULTS: circRNA microarrays showed that 469 circRNAs were differentially expressed between CCI and sham-operated rats (fold change ≥2). In all, 363 of them were significantly upregulated, and the other 106 were downregulated in the CCI group. Three of them (circRNA_013779, circRNA_008008, and circRNA_003724) overexpressed >10 times after CCI insult. Expression levels of eight circRNAs were verified using qPCR. GO analysis revealed that thousands of predicted target genes were involved in the biological processes, cellular component, and molecular function; in addition, dozens of these genes were enriched in the Hippo signaling pathway, MAPK signaling pathway, and so on. Competing endogenous RNAs analysis showed that circRNA_008008 and circRNA_013779 are the two largest nodes in the circRNA-microRNA interaction network of the top 10 circRNAs.

CONCLUSION: CCI resulted in a comprehensive expression profile of circRNAs in the spinal dorsal horn in rats. CircRNAs in the dorsal horn could be helpful to reveal molecular mechanisms of neuropathic pain.