sfn2001

Rinaman L, Wonders CP (2001) Targeted destruction of A2/C2 catecholamine neurons alters hypothalamic responses to vagal stimulation. Neuroscience 2001 Abstracts 131.4. Society for Neuroscience, San Diego, CA.

Summary: Central catecholamine (CA) pathways participate in viscerosensory modulation of hypothalamic neuroendocrine function. Different brainstem CA cell groups may relay different types of viscerosensory signals to different classes of hypothalamic effectors. The present study sought to determine the role of dorsal medullary A2/C2 neurons in hypothalamic responses to exogenous cholecystokinin (CCK), which activates gastrointestinal vagal sensory inputs to the caudal brainstem. Saporin toxin conjugated to dopamine-beta-hydroxylase antibody (anti-DbH-sap; 10 ng in 100 nl) or control toxin was microinjected unilaterally or bilaterally into the A2/C2 region of the dorsal vagal complex in adult male rats. After 10-14 days, rats were injected i.p. with CCK (10 ug/kg) and perfused with fixative 1 hr later. Brainstem and forebrain sections were processed for dual immunocytochemical detection of cFos (a marker of neural activation) and DbH (to define the lesion). Additional forebrain sections were processed for cFos and either oxytocin (OT), vasopressin (AVP), or corticotropin-releasing factor (CRF) to identify hypothalamic neurons activated by CCK. Anti-DbH-sap destroyed the majority of A2/C2 neurons within the microinjection site(s), with minimal non-specific damage. A2/C2 lesions markedly attenuated CCK-induced activation of OT neurons and, to a lesser extent, attentuated CRF activation. Conversely, CCK-induced cFos expression was significantly increased in AVP neurons. The latter effect was observed only after bilateral lesions. These results indicate that A2/C2 neurons participate in vagal sensory-mediated stimulation of OT neurons and CRF neurons, and inhibition of AVP neurons.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Luger NM, Sabino MC, Schwei MJ, Rogers SD, Pomonis JD, Keyser CP, Mach DB, Salak-Johnson J, Clohisy DR, Mantyh PW (2001) Intrathecal infusion of substance P-saporin ablates substance p receptor expressing neurons in the dorsal horn of the spinal cord and attenuates bone cancer pain. Neuroscience 2001 Abstracts 55.4. Society for Neuroscience, San Diego, CA.

Summary: Over 75% of advanced cancer patients must cope with chronic cancer pain. Interestingly, bone cancer pain is the most common and difficult to control. While current therapies are effective in alleviating many aspects of bone cancer pain, they are often accompanied by significant unwanted side effects. To better understand the population of spinal cord neurons that are involved in conveying bone cancer pain and to determine the efficacy of a novel therapeutic modality, we ablated substance P receptor (SPR)+ neurons in the spinal cord using intrathecal infusion of substance P-Saporin (SP-SAP). SP-SAP is a suicide ligand which consists of the ribosomal inactivating factor saporin conjugated to substance P, a peptidergic neurotransmitter involved in nociception. SP-SAP selectively ablates SPR+ neurons located in lamina I and III-V of the spinal cord. C3H male mice received intrathecal SP-SAP treatment 30 days prior to injection of 2472 osteosarcoma cells into the intramedulary space of a femur. Following injection, osteolytic sarcoma cells were confined within the femur by an amalgam plug. Mice were behaviorally tested 17 days post-tumor implantation and both ongoing and movement-evoked pain assessed. Ablation of SPR+ neurons in the dorsal spinal cord coincided with attenuation of both spontaneous and movement-evoked pain behaviors. These results suggest that SPR expressing neurons are involved in the development and progression of the bone cancer pain state and SP-SAP may serve as a useful therapy to treat this debilitating condition. Supported by NIH & VA.

Related Products: SP-SAP (Cat. #IT-07)