The study of pain in awake animals raises ethical, philosophical, and technical problems. We review the ethical standards for studying pain in animals and emphasize that there are scientific as well as moral reasons for keeping to them. Philosophically, there is the problem that pain cannot be monitored directly in animals but can only be estimated by examining their responses to nociceptive stimuli; however, such responses do not necessarily mean that there is a concomitant sensation. The types of nociceptive stimuli (electrical, thermal, mechanical, or chemical) that have been used in different pain models are reviewed with the conclusion that none is ideal, although chemical stimuli probably most closely mimic acute clinical pain. The monitored reactions are almost always motor responses ranging from spinal reflexes to complex behaviors. Most have the weakness that they may be associated with, or modulated by, other physiological functions. The main tests are critically reviewed in terms of their sensitivity, specificity, and predictiveness. Weaknesses are highlighted, including 1) that in most tests responses are monitored around a nociceptive threshold, whereas clinical pain is almost always more severe; 2) differences in the fashion whereby responses are evoked from healthy and inflamed tissues; and 3) problems in assessing threshold responses to stimuli, which continue to increase in intensity. It is concluded that although the neural basis of the most used tests is poorly understood, their use will be more profitable if pain is considered within, rather than apart from, the body's homeostatic mechanisms.

Animal Models of Nociception

Electrical stimulation of excitable tissue: design of efficacious and safe protocols.

Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes.

https://www.annualreviews.org/doi/pdf/10.1146/annurev.bioeng.10.061807.160518

Neural stimulation and recording electrodes.

Pathologic Basis of Diseaseby Stanley L. Robbins is really the fourth edition of hisPathology. Appropriate updating and addition enhance the otherwise identical format, sequence, writing, and illustrations. So many medical students have benefited from this source that it may be the best known general book in the field. I recommend it even more now. Like his former texts, this will be enjoyed for its readability. He clearly lays out a great deal of information. When he includes minutiae, the reasons are clear and one feels that all the material is pertinent. Robbins keeps the whole field in perspective—that is, he does not dwell so long or so heavily on pathologic anatomy or pathogenesis as to tempt the reader to overlook clinical presentation or prognosis. A great strength of the subject of pathology is that it bonds strongly with many other medical sciences and specialties and thus occupies the

Pathologic Basis of Disease

Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strate- gies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.

A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems

A novel type of nerve cuff electrode consisting of conductive segments embedded within a self-curling sheath of biocompatible insulation has been developed. This spiral nerve cuff is biased to self-wrap around peripheral nerves and possesses a 'self-sizing' property, presenting an alternative to present commercially available, fixed-size nerve cuffs that are manually wrapped around nerves and sutured shut ('split-cylinder' cuffs). Spiral cuff design and manufacture are described. The authors hypothesize that unlike traditional cuffs, the spiral cuff potentially can be implanted safely when sized to fit peripheral nerves snugly. Theoretical pressure analyzes of traditional and spiral cuffs that support this hypothesis are presented. These analyses are designed to predict the minimum CNR (cuff diameter/nerve diameter ratio) at which there is no interference with intraneural blood flow. Results of a preliminary experiment in which snug spiral cuffs were implanted on feline peripheral nerve support the prediction that they may be safe. >

/pdf/a-spiral-nerve-cuff-electrode-for-peripheral-nerve-poypgt79q2.pdf

A spiral nerve cuff electrode for peripheral nerve stimulation

Acute experiments were performed on adult cats to study selective activation of medial gastrocnemius, soleus, tibialis anterior, and extensor digitorium longus with a cuff electrode. A spiral nerve cuff containing twelve dot electrodes was implanted around the sciatic nerve, and evoked muscle twitch forces were recorded in six experiments. Spatially isolated dot electrodes in four geometries (monopolar, longitudinal tripolar, tripolar with four common anodes, and two parallel tripoles) were combined with transverse field steering current(s) from an anode(s) located 180 degrees around from the cathode(s) to activate different regions of the nerve trunk. A selectivity index was used to construct recruitment curves for a muscle with the optimal degree of selectivity. Physiological responses were correlated with the anatomical structure of the sciatic nerve by identifying the nerve fascicles innervating the four muscles, and by determining the relative positions of the electrodes and the nerve fascicles. The results indicated that the use of transverse field steering current improved selectivity. The relative performance of the various electrode arrangements is discussed. >

Selective control of muscle activation with a multipolar nerve cuff electrode

The purpose of this study was to determine the electrical properties of the encapsulation tissue that surrounds electrodes chronically implanted in the body. Two four-electrode arrays, fabricated from either epoxy or silicone rubber, were implanted in each of six adult cats for 82 to 156 days.In vivo measurements of tissue resistivity using the four-electrode technique indicated that formation of the encapsulation tissue resulted in a significant increase in the resistivity of the tissue around the arrays.In vitro measurements of tissue impedance using a four-electrode cell indicated that the resistivity of the encapsulation tissue was a function of the tissue morphology. The tight layers of fibroblasts and collagen that formed around the silicone rubber arrays had a resistivity of 627±108 Ω-cm (mean ± SD; n=6), which was independent of frequency from 10 Hz to 100 kHz, and was significantly larger than the resistivity of the epoxy encapsulation tissue at all frequencies between 20 Hz and 100 kHz. The combination of macrophages, foreign body giant cells, loose collagen, and fibroblasts that formed around the epoxy arrays had a frequency-dependent resistivity that decreased from 454±123 Ω-cm (n=5) to 193±98 Ω-cm between 10 Hz and 1 kHz, and was independent of frequency between 1 kHz and 100 kHz, with a mean value of 195 ±88 Ω-cm. The results indicate that the resistivity of the encapsulation tissue is sufficient to alter the shape and magnitude of the electric field generated by chronically implanted electrodes.

Electrical properties of implant encapsulation tissue.

Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode.

The authors review recent efforts to design stimulus waveforms for selective electrical stimulation of the nervous system. Two types of selectivity are considered. Fiber diameter selectivity refers to the ability to activate one group of nerve fibers having a common diameter without activating nerve fibers having different diameters. Spatial selectivity refers to the ability to activate nerve fibers in a localized region without activating nerve fibers in neighboring regions. The fundamental principles governing the response of excitable nerve fibers to imposed stimuli are reviewed and used to design waveforms. The emphasis of the presentation is on excitation of peripheral myelinated nerve fibers, The underlying principles, however, are broadly applicable to all excitable membranes. >

J.T. Mortimer

Papers

A spiral nerve cuff electrode for peripheral nerve stimulation

Selective control of muscle activation with a multipolar nerve cuff electrode

Electrical properties of implant encapsulation tissue.

Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode.

Stimulus waveforms for selective neural stimulation