What is 'Open'? An Economic Analysis of Open Institutions

By examining several different types of open institutions including open source software, open science, open square and (open) urban planning, this paper presents a general analysis of open institutional structure that is complementary to traditional proprietary mode. We argue that open institutions, in whatever forms, are essentially about decentralized production of a collective good (or “commons”) that relies on voluntary collaboration of highly variable human-related input. In addition to providing a general definition of open institutional structure, we submit there are two necessary conditions for open institutions. The first is the integration of consumers into production. The second condition is that the efficiency gain from “production” commons is the objective and the tragedy of anticommons becomes a serious problem. In this sense, open institutions represent a positive approach toward externality and uncertainty

Adrenal Medullary Transplants Attenuate Sensorimotor Dysfunction in Rats With Peripheral Neuropathy

Previous work in our laboratory has demonstrated that adrenal medullary transplants into the spinal subarachnoid space can alleviate neuropathic pain behaviors. The purpose of this study was to test the possibility that motor, as well as, sensory dysfunction is reduced by adrenal medullary transplants. Peripheral neuropathy was induced by a chronic constriction injury (CCI) of the sciatic nerve of rats. In addition to exaggerated responses to noxious and innocuous stimuli characteristic of peripheral nerve injury, severe impairment of hindpaw placing and grasping reflexes following CCI was observed. Two weeks following CCI, either adrenal medullary or control striated muscle tissue was implanted into the spinal subarachnoid space. Adrenal medullary, but not control transplants, produced significant restoration of hindlimb reflex function in animals with peripheral nerve injury. This was reversed by pretreatment with the α-adrenergic antagonist phentolamine, but not the opiate antagonist naloxone, suggesting a role for catecholamines secreted by the implanted cells in reflex recovery. Adrenal medullary transplants also attenuated hyperalgesia and allodynia resulting from nerve injury. These results indicate that adrenal medullary transplants can alleviate sensorimotor dysfunction consequent to peripheral nerve injury

Attenuation of formalin pain responses in the rat by adrenal medullary transplants in the spinal subarachnoid space

Previous reports have indicated that the implantation of adrenal medullary chromaffin cells into the spinal subarachnoid space can reduce both acute and chronic pain in several animal models. Recent findings suggest that acute and chronic pain alleviation may be mediated by distinct mechanisms. Since the formalin response is composed of an acute and tonic phase which can be pharmacologically distinguished, the ability of adrenal medullary implants to alter these responses was assessed. In rats with adrenal medullary transplants, both phases of the formalin response were attenuated, in contrast to control implanted animals. Suppression of the acute phase by adrenal medullary implants was reversed by the opiate antagonist naloxone, and partially reversed by the α-adrenergic antagonist phentolamine, suggesting that opioid peptides and catecholamines released by the implanted chromaffin cells contribute to the observed antinociception. However, neither antagonist altered the antinociceptive effects of adrenal medullary implants on the tonic phase of the formalin response. These results indicate that adrenal medullary implants in the spinal subarachnoid space alleviate acute and tonic pain via distinct pharmacologic mechanisms

Attenuation of NMDA-induced spinal hypersensitivity by adrenal medullary transplants

Abnormal sensory hyperexcitability consequent to peripheral injury most likely involves activation of N-methyl- d-aspartate (NMDA) receptors in the spinal cord. This activation may lead to a cascade of neuroplastic events resulting in the exaggeration of sensory responses and the persistence of pathological pain states. Recent studies in our laboratory have demonstrated that the transplantation of adrenal medullary cells into the spinal subarachnoid space can alleviate pathological pain symptoms, possibly by reducing spinal hyperexcitability. The purpose of this study was to assess spinal NMDA activation-induced hypersensitivity to noxious and innocuous stimuli, and determine whether adrenal medullary transplants can intervene favorably to reduce these responses. Animals with either adrenal medullary or control transplants were injected intrathecally with several doses of NMDA, and responses to sensory stimuli were determined over time. NMDA at all doses tested (1–50 nmol) produced significant thermal and mechanical hyperalgesia and tactile allodynia in control transplanted animals, with peak severity at 30 min post-injection. In contrast, both the severity and duration of these exaggerated sensory responses were markedly reduced in animals with adrenal medullary transplants. To assess a possible contribution of released opioid peptides and catecholamines from the transplanted chromaffin cells, animals were pretreated with opiate antagonist naloxone or α-adrenergic antagonist phentolamine. While naloxone was ineffective, the phentolamine partially attenuated, but did not completely abolish, the antinociceptive effects of the transplants. The results of these studies demonstrate that adrenal medullary grafts can reduce hypersensitivity responses to NMDA-mediated activation via α-adrenergic modulation in addition to other neuroprotective mechanisms

Suppression of neuropathic pain by a naturally-derived peptide with NMDA antagonist activity

Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser 1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management

Alterations in rat spinal cord cGMP by peripheral nerve injury and adrenal medullary transplantation

Adrenal medullary chromaffin cells implanted into the spinal subarachnoid space can reduce abnormal pain-related responses in chronic pain models. Persistent pain is thought to involve the activation of N-methyl- d-aspartate (NMDA) receptors and subsequent production of nitric oxide (NO) and cyclic guanosine 3′,5′-monophosphate (cGMP). Changes in dorsal horn levels of cGMP in the rat were determined in conjunction with alterations in pain behaviors following peripheral nerve injury and adrenal medullary transplantation. Results indicated increased spinal cGMP levels in parallel with thermal and mechanical hyperalgesia and tactile allodynia consequent to chronic constriction injury of the sciatic nerve in rats. Adrenal medullary, but not control transplants, attenuated the hyperalgesia and allodynia and decreased spinal cGMP content. These results suggest that adrenal medullary transplants may reduce abnormal pain by intervention in the spinal NMDA-NO cascade

NMDA-Induced Spinal Hypersensitivity Is Reduced by Naturally Derived Peptide Analog [Ser ] Histogranin

N-methyl-D-aspartate (NMDA) receptor activation is thought to initiate a cellular cascade of events in the spinal cord that leads to neuronal hyperactivation and exaggerated persistent pain behaviors. Previous studies have demonstrated that implantation of adrenal medullary tissue into the spinal subarachnoid space reduces abnormal pain behaviors such as hyperalgesia and allodynia, possibly by intervening in the NMDA hyperexcitability cascade. Histogranin is a 15-amino acid peptide possessing NMDA receptor antagonist activity that has been isolated from adrenal medullary tissue. The present study examined the ability of stable analog [Ser1]histogranin to reduce abnormal pain-related behaviors induced in rats by direct activation of spinal NMDA receptors. The intrathecal injection of NMDA (5.0, 10.0, 20.0 nmol) produced significant thermal and mechanical hyperalgesia and tactile allodynia in a dose-related fashion. [Ser1]histogranin injected intrathecally prior to NMDA injections dose dependently attenuated or completely blocked hyperalgesia and allodynia. In addition, [Ser1]histogranin administration following NMDA-induction of abnormal pain behaviors reversed these effects. These results demonstrate that a naturally derived adrenal medullary neuropeptide can prevent and reverse NMDA-mediated spinal hyperexcitability. The distinct profile and robust activity of [Ser1]histogranin suggest novel alternative approaches in the management of pain and other CNS disorders involving abnormal excitatory neurotransmission

Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve injury and adrenal medullary grafting

Excessive activation of N-methyl- d-aspartate (NMDA) receptors in the spinal cord consequent to peripheral injury has been implicated in the initiation of neuropathologic events leading to a state of chronic hyperexcitability and persistence of exaggerated sensory processing. In other CNS disease or injury states, NMDA-mediated neurotoxic damage is associated with a loss of NMDA receptors, and outcome may be improved by agents reducing NMDA activation. Previous findings in our laboratory have demonstrated that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can alleviate sensory abnormalities and reduce the induction of a putative nitric oxide synthase consequent to peripheral nerve injury. In order to determine changes in NMDA receptor expression in the spinal cord following peripheral nerve injury and adrenal medullary grafting, NMDA receptor binding using a high-affinity competitive NMDA receptor antagonist, CGP-39653, and NMDAR1 subunit distribution using immunocytochemistry were investigated. Two weeks following peripheral nerve injury by loose ligation of the right sciatic nerve, either adrenal medullary or striated muscle (control) tissue pieces were implanted in the spinal subarachnoid space. Binding studies revealed a marked reduction in [ 3H]CGP-39653 binding at L 4–L 5 levels ipsilateral to peripheral nerve injury in control transplanted animals. In contrast, NMDA binding was normalized in adrenal medullary grafted animals. In addition, NMDAR1 immunoreactivity was reduced in both the dorsal horn neuropil and motor neurons of the ventral horn in animals with peripheral nerve injury, while levels in adrenal medullary grafted animals appeared similar to intact controls. These results suggest that adrenal medullary transplants reduce abnormal sensory processing resulting from peripheral injury by intervening in the spinal NMDA-excitotoxicity cascade