Willie K. Dong

The role of the basal ganglia in nociception and pain

&NA; The involvement of the basal ganglia in motor functions has been well studied. Recent neurophysiological, clinical and behavioral experiments indicate that the basal ganglia also process non‐noxious and noxious somatosensory information. However, the functional significance of somatosensory information processing within the basal ganglia is not well understood. This review explores the role of the striatum, globus pallidus and substantia nigra in nociceptive sensorimotor integration and suggests several roles of these basal ganglia structures in nociception and pain. Electrophysiological experiments have detailed the non‐nociceptive and nociceptive response properties of basal ganglia neurons. Most studies agree that some neurons within the basal ganglia encode stimulus intensity. However, these neurons do not appear to encode stimulus location since the receptive fields of these cells are large. Many basal ganglia neurons responsive to somatosensory stimulation are activated exclusively or differentially by noxious stimulation. Indirect techniques used to measure neuronal activity (i.e., positron emission tomography and 2‐deoxyglucose methods) also indicate that the basal ganglia are activated differentially bo noxious stimulation. Neuroanatomical experiments suggest several pathways by which nociceptive information may reach the basal ganglia. Neuroanatomical studies have also indicated that the basal ganglia are rich in many different neuroactive chemicals that may be involved in the modulation of nociceptive information. Microinjection of opiates, dopamine and gamma‐aminobutyric acid (GABA) into the basal ganglia have varied effects on pain behavior. Administration of these neurochemicals into the basal ganglia affects supraspinal pain behaviors more consistently than spinal reflexive behaviors. The reduction of pain behavior following electrical stimulation of the substantia nigra and caudate nucleus provides additional evidence for a role of the basal ganglia in pain modulation. Some patients with basal ganglia disease (e.g., Parkinsons disease, Huntingtons disease) have alterations in pain sensation in addition to motor abnormalities. Frequently, these patients have intermittent pain that is difficult to localize. Collectively, these data suggest that the basal ganglia may be involved in the (1) sensory‐discriminative dimension of pain, (2) affective dimension of pain, (3) cognitive dimension of pain, (4) modulation of nociceptive information and (5) sensory gating of nociceptive information to higher motor areas. Further experiments that correlate neuronal discharge activity with stimulus intensity and escape behavior in operantly conditioned animals are necessary to fully understand how the basal ganglia are involved in nociceptive sensorimotor integration.

Nociceptive responses of trigeminal neurons in SII-7b cortex of awake monkeys

A cluster of trigeminal nociceptive neurons was located in the lateral sulcus on the upper bank of the frontoparietal operculum in a region bordering between cortical areas SII and 7b. These neurons were isolated in cortical cell layers IV and V-VI. All nociceptive neurons responded exclusively to noxious mechanical stimulation of cutaneous receptive fields on the face/head or intraoral tissue. Sustained noxious mechanical stimulation elicited slowly adapting responses that accurately encoded the duration of the stimulation. Prolonged discharges following removal of noxious stimulation were not observed. These nociceptive specific neurons poorly encoded graded noxious stimuli. Trigeminal somatosensory neurons within and surrounding the SII-7b cluster were not topographically organized according to divisions of the trigeminal nerve, laterality of receptive fields, or division of face/head and intraoral receptive fields. The thalamocortical, corticocortical and indirect corticolimbic connectivities of SII and area 7b and the possible role of SII-7b nociceptive neurons in learning, memory and avoidance behaviors are discussed.

Physiological properties of intradental mechanoreceptors

A major role of tooth receptors in signaling overt or impending tissue damage (nociception) has been previously established by substantial evidence from mechanical, thermal and chemical stimulation of exposed dentin. We report evidence showing that some intradental receptors in canine teeth of the cat detect mechanical transients applied to intact enamel. This new finding suggests that dental innervation may play an important non-nociceptive role in oral function such as detecting tooth contact during mastication and swallowing.

The assessment of pain by cerebral evoked potentials

Cerebral evoked potentials have been recorded by various means for nearly 100 years [ 14

Multisensory convergence and integration in the neostriatum and globus pallidus of the rat

The extracellular response properties of neurons in the caudate-putamen (CPu), globus pallidus (GP) and lateral amygdaloid nucleus (La) evoked by auditory and somatosensory stimuli were investigated. A total of 61 neurons in these areas responded either singly to somatosensory stimulation (unisensory), or to both somatosensory and auditory stimulation (multisensory). Higher rates of somatosensory stimulation reduced the response magnitude of CPu neurons more than that of GP neurons. In multisensory neurons, combined somatosensory and auditory stimulation compared to unisensory stimulation resulted in three characteristic response patterns: enhancement, depression or interaction. Temporal misalignment of the peak frequency latencies evoked by auditory and somatosensory stimulation altered the response magnitude in the majority of neurons. The response properties and anatomical connectivity of CPu and GP neurons suggest that the observed multisensory integrative effects may be used to facilitate motor responses to low intensity stimuli.

Origins of cat somatosensory far-ffield and early near-field evoked potentials

A complex pattern of potentials evoked by forelimb cutaneous nerve stimulation was recorded from the skull surface of barbiturate anesthetized cats and was resolved by computer averaging. Seven far-field components (designated I-VII) and several larger early near-field components (designated P1, N1, P2, N2 and P3) have been identified from averaged potentials. All far- and early near-field components were elicited by activation of myelinated nerve fibers. Their latency and amplitude depended entirely on the number of large myelinated nerve fibers recruited into the nerve volley. Spinal lesions showed that peripherally evoked far- and early near-field potentials were generated from both lemniscal and extralemniscal sources. Far-field and early near-field potentials were evoked either from the lemniscal system by dorsal column stimulation or from the extralemniscal system by cutaneous nerve stimulation after dorsal column lesions. These potentials were similar in configuration to those evoked by cutaneous nerve stimulation in the intact cat. Sequential rostral to caudal ablations and lesions within the lemniscal or extralemniscal system eliminated the potentials selectively. The following sites of origin were proposed: I--peripheral nerve; II (IIa)--dorsal columns; IIb--spinothalamic tract; III--dorsal column nuclei or medial lemniscus; III, IV--spinocerebellar and spinoreticular tracts; V--lateral reticular nucleus or reticulocerebellar tract; VI, VII--cerebellum; P1--lateral and medial thalamic nuclei or thalamocortical projections; N1, P2--sensorimotor cortical areas; N2, P3--association cortical areas. Lemniscal and extralemniscal far- and early near-field potentials were generated from common as well as separate sites. The latencies of somatosensory far- and early near-field potentials recorded extracranially in this study closely correlated with the latencies of local potentials recorded by others at the proposed lemniscal and extralemniscal sites of origin. The contribution of extralemniscal sources to far- and early near-field potentials and their importance to clinical measurement of somatosensory evoked potentials and diagnosis of neurological disorders are discussed.

Tooth pulp-evoked potentials in the monkey: Cortical surface and intracortical distribution

&NA; The distribution of tooth pulp‐evoked potentials (TPEPs) was characterized in the primary motor (MI), primary somatosensory (SI) and secondary somatosensory (SII) cortices of the monkey. Bipolar electrical tooth pulp stimulation elicited TPEP components P23 and N44 over SI, P26 and N72 over MI and P72, N161, P280, N420, P561 and N662 over SII. Muscular artifacts and extradental input did not affect the TPEP as demonstrated by experiments using a neuromuscular blocking agent and removal of the pulp, respectively. The short latency TPEPs recorded over SI and MI were evoked by low stimulus intensities and activation of A&bgr; nerve fibers, whereas the long latency TPEPs recorded over SII required higher stimulus intensities and the additional recruitment of A&dgr; nerve fibers. Intracortical recordings revealed polarity reversals of components P23 and N44 in area 3b, P26 and N72 in area 4 and P72, N161, P280, N420, P561 and N662 in the upper bank of the lateral sulcus (SII). Evidence presented in this study suggests that TPEPs recorded from SI and MI relate to non‐nociceptive mechanisms while TPEPs recorded from SII relate to nociceptive mechanisms.

Behavioral outcome of posterior parietal cortex injury in the monkey

&NA; Recent studies from our laboratory have characterized the response properties of trigeminal nociceptive neurons located in the posterior parietal cortex of awake monkeys, particularly in the rostral portion of the inferior parietal lobule and parietal operculum within the lateral sulcus. The stimulus intensity‐response functions of some nociceptive neurons were significantly correlated to the stimulus intensity‐escape frequency functions. The present study provides evidence that trauma to the posterior parietal cortex alters pain sensibility to the contralateral face. Although thermal pain tolerance was dramatically altered, the discriminative aspect of thermosensitivity may have remained intact. Our results complement the recent findings of clinical studies concerned with pain and damage to the posterior parietal cortex and of experimental studies concerned with painful stimulation and changes in regional cerebral blood flow. The role of the posterior parietal cortex in nociception and pain is discussed in relation to the first somatosensory area and to unilateral spatial neglect (inattention).

Cortical nociceptive responses and behavioral correlates in the monkey

Experiments were performed to characterize cerebral cortical activity and pain behavior elicited by electrical stimulation of the tooth pulp in unanesthetized monkeys. Four monkeys were trained on two different operant paradigms: two on a simple escape task and two on an appetitive tolerance-escape task. All monkeys were implanted with bipolar stimulating electrodes in the right maxillary canine tooth and subdural recording electrodes over the left primary (SI) and/or secondary (SII) somatosensory cortices. Subdural tooth pulp-evoked potentials (TPEPs) recorded over the SII consisted of components P1 (27.5 ms), N1 (40.3 ms), P2 (84.0 ms), N2 (163.5 ms), P3 (295.3 ms), and N3 (468.0 ms). The long latency component (P3-N3) was found exclusively over the SII and was elicited by high intensity stimulation. The appearance of component P3-N3 required the recruitment of A delta nerve fibers into the maxillary nerve compound action potential and was correlated with high frequencies of escape. Administration of morphine sulfate (4 mg/kg, i.m.) caused a contemporaneous reduction in escape frequency and in the amplitude of P3-N3 recorded over the SII. The relationships between TPEP amplitude, escape behavior and A delta nerve fiber activity strongly suggest that the SII is involved with nociception and pain behavior.

Neuroma pain model: Correlation of motor behavior and body weight with autotomy in rats

Abstract A rat pain model was investigated by examining the correlation of autotomy (self‐mutilation) score with motor behavior and body weight change after sciatic nerve transection, encapsulation and neuroma formation. Observations of motor behavior and body weight changes (e.g. feeding behavior) as an index of pain were considered to have several advantages over scoring the degree of autotomy. Motor activity of 14 rats (12 neuroma, 2 sham), measured using a stabilimeter, was compared on a weekly basis to autotomy scores for a total of 7 weeks after surgery. Additionally, body weight of 26 rats (20 neuroma, 6 sham surgery) was monitored for 4 weeks following surgery. While autotomy, changes in body weight and abnormalities in motor behavior were observed after surgery, no significant Spearman rank correlation coefficients were determined for any week and thus no significant relationships were found between autotomy score and motor activity or body weight. However, it was observed that rats after sham surgery gained significantly more weight than rats after sciatic nerve transection. Therefore, these results cast doubt on the validity of autotomy score as the sole index of pain.