A Study Of Neuropathic Mechanism Of Cervicogenic Pain

Objective: Headache and pain in the neck are common in clinic, it is important for elucidating the details of the neuroanatomy and neurochemistry of the nerves innervating the posterior longitudinal ligament (PLL), spinal dura, facet joint capsule and vertebral artery(VA) so to provide a basis for prevention and therapy. Materials and Methods: 12 male Sprague-Dawley rats were divided into Sympathectomy rats (A group n=6) and Non-Sympathectomy rats(B group n=6),Bilateral cervical sympathetic chain and ganglia were removed in A group, and the operation in B group is in the same manner with A group but sympathetic chain and ganglia were not removed.one day after operation all the rats were perfused under deep anesthesia and the posterior longitudinal ligament (PLL), the spinal dura mater, the facet joint capsules and the vertebral artery were resected and processed for SP and TH immunohistochemistry. Immunoreactive(IR) fibers were traced using a light microscope and the positive area of the immunoreactive fibers were calculated.Results: tissues around the cervical vertebrae innervated by the SP-IR fibers and TH-IR fibers which comprises the dura mater, posterior longitudinal ligaments, facet joint capsule and vertebral artery. The innervation of the dura mater mainly located in the epiradicular sheath and ventral side and immunoreactive fibers on the PLL are mainly in the intervertebral portion,the majority of nerve fibers distributed on the external membrane and median membrane of VA were sympatheticpost-ganglia fiers. The numbers of TH-IR fibers on all tisues were significant difference after Sympathectomy(p<0.01).Conclusion: Neuropeptide SP was approved to co-localize with NE in the tissues around cervical spinal,it is suggested that these tissues are related to cervicogenic pain, and Sympathetic nerves may play an important role for regulations of primary afferent.A large number of SP-IR fibers were found in the dorsal root ganglion area, and Radicular pain in the upper extremities may be induced by stimulation of the sensory fibers of the epiradicular sheath alone. A majority of sympathetic fibers were distributed in the external and median membrane of VA and mechanical pressure or inflammation of the tissues may cause spasm of VA and vertebrobasilar insufficience(VBI). Objective: To observe the distribution of noradrenergic nerves and peptidergic nerves in spinal ganglion(DRG) and superior cervical ganglion(SG), and to investigate the origin of noradrenergic nerves in spinal ganglion and the interaction in regulating primary sensory afferent between DRG and SG. Materials and Methods: 36 male Sprague-Dawley rats were divided into six groups,6 rats in A group were perfused,DRGs from C3 to C5 and SG were removed for SP and TH immunohistochemical observations;The fiber connection between DRG and SG were observed by the HRP anterotracing technique in B group(6 rats) and Bb retrotracing technique in C group(6 rats);The liminal value of mechanical contractive leg in E group(6 rats) were measured after the bilateral sympathetic chain and ganglia were removed; nonoperated rats in F group(6 rats) were used as normal control subjects. Conclusion: Postsympathetic nerve fibers could directly reach the DRG and contact with DRG neurons,through which primary somatic sensory afferent message could be regulated;Futhermore what SP immunoreactive fibers in the SG came from primary sensory neurons in the DRG suggested that a regulation mechenism between DRG neurons and SG neurons outside the central nervous system exists; cervical sympathectomy raised the threshold of pain sensitivity. Objective: To investigate the pattern of innervation of the cervical facet joint and to determine the pathways from the facet joint to dorsal root ganglions in order to clarify the causes of diffuse neck pain headache and shoulder pain and provide a basis for therapy after facet joint lesions. Method: 39 male Sprague-Dawley rats in three groups were used, including Non-Sympathectomy rats (Group A; n=18), Sympathectomy rats (Group B; n=18) and control rats (Group C; n=3). 5% Bisbenzimide(Bb) were injected into the C1-2, C3-4 and C5-6 facet joints in group A and group B while Bb was replaced with 0.9% saline in group C. Numbers of the labeled neurons in dorsal root ganglions (DRG) from C1 to C8 and sympathetic ganglions(SG) were counted and statistic analysis was made. Result: Neurons labeled with Bb were present in both DRG and SG in group A, which were present from C1-C8 DRG after C1-2 and C3-4 Bb administration and from C3-C8 after C5-6 Bb administration. The number of Bb(+) neurons in group B was not significantly different in injected level from that in group A, but in the other levels Bb(+) neurons was significantly less than that in group A; No labeled neurons was found in group C. Conclusion: The innervation of the cervical facet joint were derived from the both sensory and sympathetic nervous system, DRG were associated with SG through nerve fibers. Blockade of other spinal nerves or sympathetic ganglions is possibly effective for patients with facet disorders. Objectives: Trigeminal ganglia is closely associate with upper spinal dorsal root in anatomy and function.The study explored the fiber connection between C1-3 facet joint and trigeminal ganglia , as well as peripheral mechanism of cervicogenic headache stemming from the C1-3 facet joint. Methods:40 male Sprague-Dawley rats were randomly divided into five groups , 5% Bisbenzimide(Bb) were respectively injected into the C1-2(A group), C2-3(B group) ,C3-4(C group) and C4-5(D group) facet joints on left side , Bb labeled cells were observed after 8 hours, and in E group the distribution of SP-IR(immunoreactive) cells were detected by immunocytochemical technique . Results: neurons labeled with Bb were present in A,B,C and D group , the number of Bb labeled neurons in C group was significantly less than that in A and B group while in D group no Bb labeled neurons was found; and SP-IR neurons were unevenly located in the trigeminal peripheral root ,both Bb labeled neurons and SP-IR neurons were composed primarily of middle and small sized cells contained a higher percentage of thin myelinated and unmyelinated fibers. Conclusions :The innervation of C1-3 facet joint partly stemming from collateral branches of trigeminal sensory root or directly peripheral root,injuries or instability of the atlanto-occipital joint ,the lateral atlanto-axial joint and the C2-3 zygapophysial joint can cause occiput and regions innervated by the trigeminal nerve pain.It indicated that a peripheral mechanism of cervicogenic headache outside central system existed, which is differ from referred pain induced by convergence.. Objective: NPY and its receptors play a modulatory role in processing nociceptive information, Peripheral nerve injury can induce a marked plasticity in the expression of the NPY and its receptor mRNA, However, the exact relations between NPY and its receptors that are regulated in DRG neurons after cervical nerve injury have been studied only to a limited extent. NPY and its receptors phenotype of DRG neurons after nerve injury were observed at present study so as to demonstrate the peripheral mechnisms of neuropathic pains and provide a target for developing new drugs.Material and methods: Neuropathic pains model was established in Sprague-Dawley rats,Rats in SNL group and sham group and control group were perfused and left C5 and C6 DRGs were removed respectively 7 and 14 days after operation,The expression of NPY and Y1 and Y2 receptors in gene and protein level were detected by immunofluorescence and transcription polymerse chain reaction(RT-PCR) and western blotting.Results: In sham and control DRGs ,no NPY-immunoreactive (IR) fibers and cell bodies could be observed while Y1R and Y2R signals were visualized,after nerve injuries strongly labeled NPY-immunoreactive cells were Detected and the expression of Y1R and Y2R showed upregulated, Y1R immunoreactive was prominent in a population of small-sized cells and Y2R was in a large cells.NPY and Y1R or Y2R double-labeled neuron mainly were large cells. In sham and control DRGs,there were no expression or in a low level expression of NPY mRNA and protein, significant differences were noticed after nerve injuries(P<0.01).Conclusions: Y1R and Y2R may play an important role in regulation of hyperalgesia; NPY manage nociceptive pain may act on Y1 and Y2 expressed and its receptors represent an attractive target for analgesics that may retain their effectiveness in neuropathic pain states.Y2R was a key molecule in neuropatic pain at which to design a new drug to aim directly may carry out gene therapy for neuropathic pain.