Dorsal root ganglia may be reservoirs of viral infection in multiple sclerosis

Abstract

There are presently two competitive theories that attempt to explain the etiology of multiple sclerosis (MS). Briefly summarized, they are: 1. An infection, probably of viral type, may attack the oligodendroglia of the central nervous system; or, 2. An autoimmune process may begin with an infection of the peripheral lymphatic immune system, producing antibodies that cross the blood-brain barrier, leading to myelinoclasia. Since 1935, research has been directed toward myelin of the central nervous system and the myelin sheaths of peripheral nerve; however, dorsal root and cranial sensory ganglia (DRG) have apparently not been studied. The present hypothesis states that an infectious agent (probably viral) finds privileged sanctuary in the dorsal root and cranial sensory ganglia (DRG): thereafter periodically invading the spinal cord, brain, or peripheral nerve. Previously reported erratic spinal fluid viral titers and cultures can be explained by differences in the anatomy of the DRG in which there is a variable and limited contact of spinal fluid with sensory ganglia. Clues to this hypothesis were noted by the author during routine neurological examinations of patients with MS, in which sensory signs and symptoms were frequently encountered. This clinical observation has also been reported by others who found such symptoms in 75% of MS patients, ranking second only to incoordination.

Experimental autoimmune encephalomyelitis-induced upregulation of tumor necrosis factor-alpha in the dorsal root ganglia

“…37,38 These findings support the bidirectional trafficking of protein and/or mRNA between the DRG and the spinal cord, and they correlate well with our current experimental findings and the subsequent DRG model of MS-induced NPP described in Figure 7. Our experimental finding linking the DRG to the development of MS-induced NPP is supported by previous postulated theories proposed by Nelson (1992Nelson ( , 1993). 10,39 In addition, the pathogenic effects of TNFa via intracellular signaling pathways that promote inflammatory and/or injury-induced activation of DRG are well established.…”

“…Our experimental finding linking the DRG to the development of MS-induced NPP is supported by previous postulated theories proposed by Nelson (1992Nelson ( , 1993). 10,39 In addition, the pathogenic effects of TNFa via intracellular signaling pathways that promote inflammatory and/or injury-induced activation of DRG are well established. 40 TNFa acts via two receptors: the p55 TNFR1 and the p75 TNFR2.…”

“…9 Approximately 75% of all patients with MS suffer NPP, placing it as the second worst disease-induced symptom. 10,11 Sensory symptoms such as pins and needles, burning, shooting, and/or stabbing pain with or without throbbing and numbness are characteristic symptoms of NPP. 12 Sensory abnormalities have been reported to be the first symptom described by many patients with MS before diagnosis.…”

Downregulation of the p75 Neurotrophin Receptor in Tissue Culture and In Vivo, Using β-Cyclodextrin-Adamantane-Oligonucleotide Conjugates

“…Indeed, this may already occur in nature. It has been hy¬ pothesized that DRG can act as reservoirs for infectious agents that may later attack the CNS and PNS (Nelson, 1993).…”

DNA Vaccination against Theiler’s Murine Encephalomyelitis Virus Leads to Alterations in Demyelinating Disease

“…Multiple sclerosis (MS) is the most common human demyelinating disease, affecting thousands of individuals a year, with an estimated 2 million cases worldwide (12,26). Several etiologies have been proposed for the disease, but none has clearly been established.…”