Howard Fields, MD, PhD

Professor Emeritus

Neurology and Physiology

[email protected]

Neural Circuitry of Motivation

My interest in opioid analgesia and addiction is an outgrowth of my research on pain, pain modulation and reward circuits. Both chronic pain and addiction represent dysfunction of neural mechanisms of decision making. My laboratory is closed, however, I am working in collaboration with other UCSF laboratories utilizing in vivo and in vitro electrophysiology and behavioral pharmacology to study mesolimbic circuits involved in goal directed behaviors. Our joint interest is on how opioid regulation of synaptic function modulates reward seeking and response to punishment.

Publications:

International Association for the Study of Pain publications over the 50-year span.

A deeper dive into top-down control of pain and itch.

Optimal opioid treatment requires a consensual approach.

Optimal opioid treatment requires a consensual approach.

Pain modulates dopamine neurons via a spinal-parabrachial-mesencephalic circuit.

Onset hyperalgesia and offset analgesia: Transient increases or decreases of noxious thermal stimulus intensity robustly modulate subsequent perceived pain intensity.

A Midbrain Circuit that Mediates Headache Aversiveness in Rats.

How expectations influence pain.

Two delta opioid receptor subtypes are functional in single ventral tegmental area neurons, and can interact with the mu opioid receptor.

Cortico-Accumbens Regulation of Approach-Avoidance Behavior Is Modified by Experience and Chronic Pain.

Mu Opioid Receptor Actions in the Lateral Habenula.

Ventral Pallidum Neurons Encode Incentive Value and Promote Cue-Elicited Instrumental Actions.

Mu-opioid receptor activation in the medial shell of nucleus accumbens promotes alcohol consumption, self-administration and cue-induced reinstatement.

Alterations in the rostral ventromedial medulla after the selective ablation of µ-opioid receptor expressing neurons.

Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain.

Understanding opioid reward.

Direct bidirectional µ-opioid control of midbrain dopamine neurons.

Neuroscience. More pain; less gain.

Parceling human accumbens into putative core and shell dissociates encoding of values for reward and pain.

Capturing the aversive state of cephalic pain preclinically.

Intra-VTA deltorphin, but not DPDPE, induces place preference in ethanol-drinking rats: distinct DOR-1 and DOR-2 mechanisms control ethanol consumption and reward.

Catechol-O-methyltransferase genotype modulates opioid release in decision circuitry.

Opioid modulation of ventral pallidal afferents to ventral tegmental area neurons.

Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry.

Ventral tegmental area glutamate neurons: electrophysiological properties and projections.

Identification of rat ventral tegmental area GABAergic neurons.

Dopamine, corticostriatal connectivity, and intertemporal choice.

Corticostriatal functional connectivity predicts transition to chronic back pain.

Alcohol self-administration, anxiety, and cortisol levels predict changes in delta opioid receptor function in the ventral tegmental area.

Varenicline decreases alcohol consumption in heavy-drinking smokers.

Pain and the primary somatosensory cortex.

Alcohol consumption induces endogenous opioid release in the human orbitofrontal cortex and nucleus accumbens.

Prefrontal cortex mediates extinction of responding by two distinct neural mechanisms in accumbens shell.

Engagement of descending inhibition from the rostral ventromedial medulla protects against chronic neuropathic pain.

A novel opioid receptor-mediated enhancement of GABAA receptor function induced by stress in ventral tegmental area neurons.

Nucleus accumbens medium spiny neurons target non-dopaminergic neurons in the ventral tegmental area.

Interaction between family history of alcoholism and Locus of Control in the opioid regulation of impulsive responding under the influence of alcohol.

Roles of nucleus accumbens core and shell in incentive-cue responding and behavioral inhibition.

Lesion of the rostral anterior cingulate cortex eliminates the aversiveness of spontaneous neuropathic pain following partial or complete axotomy.

The doctor's dilemma: opiate analgesics and chronic pain.

Ask the experts: What has the establishment of multidisciplinary pain centers done to improve the management of chronic pain conditions?

Reliability in the identification of midbrain dopamine neurons.

Isolating event-related neuronal responses by deconvolution.

Reply: Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy?

Predicting value of pain and analgesia: nucleus accumbens response to noxious stimuli changes in the presence of chronic pain.

A pause in nucleus accumbens neuron firing is required to initiate and maintain feeding.

Unmasking the tonic-aversive state in neuropathic pain.

Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy?

The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses.

Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network.

Delta-opioid receptor expression in the ventral tegmental area protects against elevated alcohol consumption.

Naltrexone aversion and treatment efficacy are greatest in humans and rats that actively consume high levels of alcohol.

Midbrain dopamine neurons: projection target determines action potential duration and dopamine D(2) receptor inhibition.

Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons.

Dorsomedial prefrontal cortex contribution to behavioral and nucleus accumbens neuronal responses to incentive cues.

Immediate reward bias in humans: fronto-parietal networks and a role for the catechol-O-methyltransferase 158(Val/Val) genotype.

Cue-evoked encoding of movement planning and execution in the rat nucleus accumbens.

Understanding how opioids contribute to reward and analgesia.

Should we be reluctant to prescribe opioids for chronic non-malignant pain?

The Asp40 mu-opioid receptor allele does not predict naltrexone treatment efficacy in heavy drinkers.

Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement.

Cholecystokinin is necessary for the expression of morphine conditioned place preference.

How prior reward experience biases exploratory movements: a probabilistic model.

Rat nucleus accumbens neurons persistently encode locations associated with morphine reward.

Endogenous opioid blockade and impulsive responding in alcoholics and healthy controls.

The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?

Endogenous opioids encode relative taste preference.

Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study.

Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine.

Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex.

Inhibitions of nucleus accumbens neurons encode a gating signal for reward-directed behavior.

Impulsive responding in alcoholics.

Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial.

A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats.

Fibromyalgia from the perspective of neuropathic pain.

Encoding of palatability and appetitive behaviors by distinct neuronal populations in the nucleus accumbens.

Both kappa and mu opioid agonists inhibit glutamatergic input to ventral tegmental area neurons.

Dissociation of the role of nucleus accumbens dopamine in responding to reward-predictive cues and waiting for reward.

Contrasting effects of dopamine and glutamate receptor antagonist injection in the nucleus accumbens suggest a neural mechanism underlying cue-evoked goal-directed behavior.

State-dependent opioid control of pain.

A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism.

The ventral tegmental area is required for the behavioral and nucleus accumbens neuronal firing responses to incentive cues.

Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal.

Local application of the cannabinoid receptor agonist, WIN 55,212-2, to spinal trigeminal nucleus caudalis differentially affects nociceptive and non-nociceptive neurons.

Cue-evoked firing of nucleus accumbens neurons encodes motivational significance during a discriminative stimulus task.

Firing of nucleus accumbens neurons during the consummatory phase of a discriminative stimulus task depends on previous reward predictive cues.

Peptidergic nociceptors of both trigeminal and dorsal root ganglia express serotonin 1D receptors: implications for the selective antimigraine action of triptans.

Kappa-opioid agonists directly inhibit midbrain dopaminergic neurons.

Kappa opioid receptor activation in the nucleus accumbens inhibits glutamate and GABA release through different mechanisms.

National Institutes of Health Workshop: reflex sympathetic dystrophy/complex regional pain syndromes--state-of-the-science.

Capsaicin evoked pain and allodynia in post-herpetic neuralgia.

Pain: an unpleasant topic.

Comments on Thurston and Randich.

Do benzodiazepines have a role in chronic pain management?

Activity of nociceptive modulatory neurons in the rostral ventromedial medulla associated with volume expansion-induced antinociception.

Treatment of inflammatory, neuropathic and sympathetically maintained pain in a patient with Sjögren's syndrome.

Post-herpetic neuralgia: the relation of pain complaint, sensory disturbance, and skin temperature.

Topical lidocaine reduces pain in post-herpetic neuralgia.

Can opiates relieve neuropathic pain?

Sources of variability in the sensation of pain.

Synergy between the antinociceptive effects of intrathecal clonidine and systemic morphine in the rat.

Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord.

Naloxone fails to antagonize nitrous oxide analgesia for clinical pain.

Analgesic responses to morphine and placebo in individuals with postoperative pain.