Evaluation of brain activation related to resting pain using functional magnetic resonance imaging in cynomolgus macaques undergoing knee surgery.

Purpose: Functional magnetic resonance imaging (fMRI) visualizes hemodynamic responses associated with brain and spinal cord activation. Various types of pain have been objectively assessed using fMRI as considerable brain activations. This study aimed to develop a pain model in cynomolgus macaques undergoing knee surgery and confirm brain activation due to resting pain after knee surgery.

Potential sex differences in activation of pain-related brain regions in nonhuman primates with a unilateral spinal nerve ligation.

The lack of truly robust analgesics for chronic pain is owed, in part, to the lack of an animal model that reflects the clinical pain state and of a mechanism-based, objective neurological indicator of pain. The present study examined stimulus-evoked brain activation with functional magnetic resonance imaging in male and female cynomolgus macaques following unilateral L7 spinal nerve ligation and the effects of clinical analgesics pregabalin, duloxetine, and morphine on brain activation in these macaques. A modified straight leg raise test was used to assess pain severity in awake animals and to evoke regional brain activation in anesthetized animals.

Regional brain activation during rectal distention and attenuation with alosetron in a nonhuman primate model of irritable bowel syndrome.

Greater understanding of the mechanism that mediates visceral pain and hypersensitivity associated with irritable bowel syndrome (IBS) would facilitate the development of effective therapeutics to manage these symptoms. An objective marker associated with the underlying mechanisms of visceral pain and hypersensitivity could be used to guide therapeutic development. The current study examined brain activation evoked by rectal distention with functional magnetic resonance imaging (fMRI) in a cynomolgus macaque model of visceral hypersensitivity.

Pharmacological modulation of brain activation to non-noxious stimulation in a cynomolgus macaque model of peripheral nerve injury.

In vivo neuroimaging could be utilized as a noninvasive tool for elaborating the CNS mechanism of chronic pain and for elaborating mechanisms of potential analgesic therapeutics. A model of unilateral peripheral neuropathy was developed in the cynomolgus macaque, a species that is phylogenetically close to humans. Nerve entrapment was induced by placing a 4 mm length of polyvinyl cuff around the left common sciatic nerve.

Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates.

A limitation of currently used preclinical models of colitis is that disease and treatment assessment methods differ from clinically used methods. Thus, a modified Mayo score and an endoscopic index (EI) were developed for use in cynomolgus macaques with 0.25% dextran sulfate sodium (DSS)-induced ulcerative colitis.

Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study.

Introduction: There is currently a lack of translatable, preclinical models of low back pain (LBP). Chymopapain, a proteolytic enzyme used to treat lumbar intervertebral disc (IVD) herniation, could induce discogenic LBP. The current study developed a behavioral model of discogenic LBP in nonhuman primates.

Pharmacologic Modulation of Noxious Stimulus-evoked Brain Activation in Cynomolgus Macaques Observed with Functional Neuroimaging.

Maintaining effective analgesia during invasive procedures performed under general anesthesia is important for minimizing postoperative complications and ensuring satisfactory patient wellbeing and recovery. While patients under deep sedation may demonstrate an apparent lack of response to noxious stimulation, areas of the brain related to pain perception may still be activated. Thus, these patients may still experience pain during invasive procedures.

Distinguishing analgesic drugs from non-analgesic drugs based on brain activation in macaques with oxaliplatin-induced neuropathic pain.

The antineoplastic agent oxaliplatin is a first-line treatment for colorectal cancer. However, neuropathic pain, characterized by hypersensitivity to cold, emerges soon after treatment. In severe instances, dose reduction or curtailing treatment may be necessary.

Pain-related behavior and brain activation in cynomolgus macaques with naturally occurring endometriosis.

Study Question: Can pain be objectively assessed in macaques with naturally occurring endometriosis?

Summary Answer: Behavioral, pharmacological and in vivo brain imaging findings indicate that pain can be quantified in macaques with endometriosis.

What Is Known Already: Endometriosis is characterized by abdominopelvic hypersensitity. The mechanism by which endometriosis evokes pain is largely unknown, as currently available analgesics offer limited pain relief.

Pain-Related Behavior and Brain Activation in a Cynomolgus Macaque Model of Postoperative Pain.

Background: Inadequate postoperative pain management could lead to persistent pain and this is, in part, due to incomplete understanding of the mechanism of postoperative pain. Currently available rodent models may have limited translatability to clinical postoperative pain. Thus, a preclinical model of postoperative pain was developed in the cynomolgus macaque, a species that is phylogenetically closer to humans than rodents.

Antinociceptive effect of clinical analgesics in a nonhuman primate model of knee osteoarthritis.

A number of potential analgesic pharmacotherapies developed in preclinical osteoarthritis animal models have failed clinical trials. A possible basis for the lack of translation of preclinical findings to clinical efficacy is the use of a preclinical species that is distinct from that of humans. The current study tested clinical analgesics in a nonhuman primate model of knee osteoarthritis.

Pharmacological comparison of a nonhuman primate and a rat model of oxaliplatin-induced neuropathic cold hypersensitivity.

Oxaliplatin is a first-line treatment for colorectal cancer. However, shortly following treatment, cold-evoked hypersensitivity appears in the extremities and over time, the pain is such that oxaliplatin dosing may need to be markedly reduced or even terminated. There is currently a lack of efficacious treatments for oxaliplatin-induced peripheral neuropathy, which is due in part to the difficulty in translating findings obtained from preclinical rodent models of chemotherapy-induced peripheral neuropathy.

Synthesis and evaluation of [11C]FR194921 as a nonxanthine-type PET tracer for adenosine A1 receptors in the brain.

This report describes the synthesis of [11C]2-(1-methyl-4-piperidinyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone ([11C]FR194921), a highly selective, nonxanthine-type adenosine A(1) receptor antagonist, used in brain imaging in rats and conscious monkeys as a potential novel PET tracer. [11C]FR194921 was successfully synthesized in 19 min after [11C]CH3I formation. The radiochemical yield was 38+/-3%; and radioactivity was 4.

Characterization of a novel thrombotic middle cerebral artery occlusion model in monkeys that exhibits progressive hypoperfusion and robust cortical infarction.

In an attempt to establish a thrombotic middle cerebral artery (MCA) occlusion model using cynomolgus monkeys, we measured the blood flow in the main MCA tract and cerebral cortex, brain damage, and neurological deficits, and compared them with those of mechanical MCA occlusion model. Thrombotic occlusion was induced photochemically by green light application on the MCA following rose bengal treatment; mechanical occlusion was induced by MCA clipping for 3h. Patency of the main MCA tract showed two patterns in the thrombotic model: permanent occlusion or cyclical flow reduction (CFR).