Projected pain is felt in the peripheral distribution of the same nerve that mediates the primary nociceptive input. Pain resulting from noxious stimulation of a sensory root or a major nerve trunk is felt in the exact anatomic distribution of that nerve. An example is the radicular pain of posterior root compression. It has been assumed that compression due to herniation of an intervertebral disc produces prolonged firing in the injured sensory fibers. It should be noted, however, that acute peripheral nerve compression is usually painless and rarely lasts more than a few seconds. It is likely, therefore, that radicular pain is felt in the peripheral structures through activation of deeper interneurons.18 The mechanism, however, seems to be different from that of central excitation, in that projected pain follows a more precise anatomic pattern relative to the peripheral distribution, while central excitation pain is felt in a reference zone that is only segmentally related to the primary pain source. Projected sensory nerve pain is primarily neurogenous and follows dermatome mapping faithfully. Examples of projected pain include paroxysmal neuralgia, peripheral neuritis, herpes zoster, and postherpetic neuralgia.

It has long been known that noxious stimulation of a motor root or major motor nerve also induces pain, but of a different type that is felt in different areas. Rather than the bright, burning, neuropathic pain felt in the dermatome distribution, motor nerve pain is sensed as dull, deep somatic pain diffusely located in the muscles innervated by that nerve.¹⁹ Such pain is now explicable on the basis of afferent neurons that are present in the motor nerves. Undoubtedly, such pain should be classified as projected pain, even though it displays a deep somatic rather than neuropathic quality and follows a motor nerve route rather than a dermatome field. Although the neural mechanisms have not been identified, it is likely that interneurons are involved in a manner similar to that for projected sensory nerve pain. It likewise differs from the heterotopic pain of referred pain.

Projected pains may be accompanied by areas of secondary hyperalgesia that are hypersensitive to stimulation without an appreciable reduction in the local pain threshold. Whatever the mechanism responsible for this phenomenon, it is likely similar to that of secondary hyperalgesia of central hyperexcitability, as described in the next section.

Referred pain is a spontaneous heterotopic pain that is felt in an area innervated by a different nerve than the one that mediates the primary pain. Since it is spontaneous, referred pain occurs without provocation at the site of pain and is wholly dependent upon the original source of pain. The reason for this dependence is because the original source of nociceptive input produces a sensitization of interneurons that is responsible for this type of heterotopic pain.20^{,21,22,23,24,25} Since the sensitization of interneurons (also called central excitatory effects) is very important in understanding heterotopic pains, it is worthwhile to discuss this phenomenon at this time.

Referred pain due to central sensitization is initially wholly spontaneous as far as the site of pain is concerned. It is not accentuated by provocation of the site where the pain is felt; it is accentuated only by manipulation of the primary pain source (see Fig 4-2). It is dependent on continuation of the primary initiating pain and ceases immediately if the primary pain is arrested or interrupted. Anesthesia of the structure where the referred pain is felt does not arrest the pain.³⁸ Only by anesthesia of the neural pathway that mediates the primary pain can the referred pain be arrested.³⁹

It should be noted that although the primary initiating pain is of the deep somatic type, the secondary referred pain may be felt in either deep or superficial structures. This may present a bizarre clinical picture. When reference is felt superficially, it must be differentiated from superficial somatic pain and from projected neuropathic pain. When it is felt deeply, it must be differentiated from other deep somatic pains.

Referred pain does not occur haphazardly, but in fact follows three clinical rules. Referred pain most frequently occurs within a single nerve root, passing from one branch to another. The trigeminal nerve is a good illustration, since it has three major branches. For example, when a mandibular molar presents with a source of pain (eg, caries) it is not uncommon to have the patient report that a maxillary molar is also painful. In this case, the mandibular branch of the trigeminal nerve is referring pain to the maxillary branch of the same nerve.

Fig 4-3 Dermal segmentation as represented by Netter and based essentially on the work of Keegan. (From Netter FH. The CIBA Collection of Medical Illustrations. Indianapolis: Curtis, 1953. Used with permission.)

Fig 4-4 The orderly metameric arrangement of dermatomes becomes apparent if we visualize a man in the quadruped position. (From Finneson BE. Diagnosis and Management of Pain Syndromes, ed 2. Philadelphia: Saunders, 1969. Used with permission.)

This is a fairly common occurrence with dental pain. Generally, if the pain is referred to another distribution of the same nerve, it does so in a “laminated” manner. This lamination follows the pattern of the dermatomes. A dermatome is a sensory root field on the skin where pain is felt when a particular neural segment mediates a painful sensation. These have been well charted (Fig 4-3). Each nerve has a corresponding dermatome, but there is considerable overlapping. The upright posture of humans causes some confusion in dermatome arrangement, especially in the extremities. They are better visualized with the subject in the quadruped position (Fig 4-4). This places them in a more logical metameric arrangement and helps considerably to identify the proper segmental relationships. ⁴⁰

Trigeminal lamination patterns are determined by the manner in which the primary afferent neurons enter in the spinal tract nucleus. According to Kunc,^41,42 the location of trigeminal nociceptive terminals within the nucleus caudalis is as follows:

1. The fibers from tissues near the sagittal midline of the face terminate highest in the nucleus (cephalic).
2. The fibers from tissues located more laterally terminate lowest in the nucleus (caudal).
   

   Fig 4-5 Graphic depiction of the spinal trigeminal nucleus and its relationship with incoming sensory input. Note the laminated pattern of innervation from the facial structures into the spinal tract nucleus. These laminated patterns reflect the patterns of referred pain commonly felt in the orofacial structures.

3. The intermediate fibers terminate intermediately in the nucleus (Fig 4-5). This laminated arrangement of facial innervation appears to coincide with Finneson’s metameric arrangement of the dermatomes in the quadruped position.⁴⁰

This grouping of the terminals of the primary trigeminal neurons should influence the location of clinical effects of central excitation, especially with regard to referred pain. It probably accounts for some effects not otherwise readily explained. Kawamura and Nishiyama showed that a molar tooth can project pain to a canine, and a canine can project to an incisor, which confirms the vertical lamination just cited.⁴³

Simply speaking, this means that incisors refer to incisors, premolars to premolars, and molars to molars on the same side of the mouth. In other words, molars do not refer pain to incisors or incisors to molars.

The second clinical rule is that referred pain in the trigeminal area rarely crosses the midline unless it originates at the midline. For example, pain in the right temporomandibular joint will not likely cross over to the left side of the face, nor will right molar referred pain cross to a left molar. However, this is not true in the cervical region or below. Cervicospinal pain can be referred across the midline, although it most commonly stays on the same side as the source.

A third clinical rule of referred pain is that if the referred pain is felt outside the nerve that mediates the pain, it is generally felt cephalic to the nerve (upward, toward the head) and not caudally. Clinically, this means that deep pain felt in the sacral area maybe be referred to the lumbar area, as well as lumbar to thoracic, thoracic to cervical, and cervical to trigeminal. Rarely will trigeminal pain refer to the cervical region. Only very intense primary pain causes excitatory effects in a segment caudal to the site of initiating input.^44,45

Secondary hyperalgesia

Hyperalgesia is defined as increased sensitivity to stimulation at the site of pain. Primary hyperalgesia occurs as the result of a lowered pain threshold (sensitization) in the peripheral structures, resulting presumably from the presence of algogenic substances such as bradykinin, potassium, histamine, and 5HT (see chapter 3). Secondary hyperalgesia is different. It is an increased response to stimulation at the site of pain in the absence of any local cause.⁴⁶ It may occur with or without accompanying referred pain.

Secondary hyperalgesia is also different from referred pain in that it occurs in response to stimulation (provocation) at the site of pain, while referred pain cannot be increased at the site of pain. It is wholly dependent on the source of pain. Both referred pain and secondary hyperalgesia are initiated by deep pain input and remain dependent upon the continuation of such input. They differ, however, in that secondary hyperalgesia persists for a while after the primary pain ceases. Thus, analgesic blocking of the primary pain site does not immediately arrest the hyperalgesia as it does referred pain.

As with referred pain, secondary hyperalgesia may be felt in either superficial or deep structures. Superficial secondary hyperalgesia is felt as sensitive skin, scalp, hair, or gingiva. Deep secondary hyperalgesia is sensed as an area of palpable tenderness, discomfort due to functional manipulation, or hypersensitive or tender teeth.

There are two explanations for the occurrence of secondary hyperalgesia. The first is that related to the sensitization of the second-order neuron. As central sensitization occurs, even normal input can be misinterpreted as noxious.^47,48 Therefore, even input carried by the nonnoxious A-beta fibers can be felt as pain. When this occurs, even light touch to the face becomes painful. Pain produced by normally nonpainful stimuli is called allodynia.

A second explanation for secondary hyperalgesia is one that addresses a local cause produced by neurogenic inflammation. As discussed in the last chapter, tissue injury initiates the inflammatory process, which in turn sensitizes neighboring neurons. This is called primary hyperalgesia. With central sensitization, the primary afferent neuron can antidromically release excitatory neurotransmitters (eg, SP) into peripheral tissues, increasing the sensitivity of the primary nociceptors (neurogenic inflammation). When this occurs there can be a small central area of hyperemia, indicating some local tissue reaction. In this flare area of an axon reflex, the pain threshold is lowered, thus indicating that this portion of the hyperalgesic area reflects local tissue change. The entire area of sensitivity, however, extends far beyond the hyperemic zone. The wider area represents true secondary hyperalgesia that is dependent on the continuation of primary deep pain impulses. ⁴⁵ Analgesic blocking of the source of deep pain that is creating the secondary hyperalgesia does not in fact immediately decrease the total discomfort, presumably because of the flare area that is present.^49,50 Anesthetic blocking of the region of primary hyperalgesia will immediately eliminate the pain since the cause is local.

At a clinical level, superficial secondary hyperalgesia usually presents no great problem because there is an obvious lack of local cause. Deep secondary hyperalgesia, however, cannot be distinguished from primary hyperalgesia on the basis of manual palpation or functional manipulation (see chapter 8). Special diagnostic effort is required to make this judgment, which is important therapeutically. It should be noted that palpable tenderness or deep discomfort from functional manipulation identifies only a site of pain, not a source of pain. Whether such an identified site of pain is primary hyperalgesia from a local cause such as inflammation or a heterotopic manifestation of deep pain input located elsewhere is a judgment that must precede definitive therapy.

A common efferent effect secondary to constant deep pain is a reflex excitation of the muscle, which slightly modifies its functional activity51(Fig 4-6). Deep pain input seems to activate a protective response of muscle to limit the movement of the painful part. This response is normal and likely protective in nature. It does not represent pathology. It is interesting to note that, in the presence of deep pain, the antagonist muscles appear to become activated in an attempt to limit activity of the agonist muscle.^52,53 This phenomenon is called co-contraction⁵⁴ and has previously been referred to as protective muscle splinting. The exact mechanisms involved will be discussed in later chapters. It is sufficient to say at this time that deep pains that produce central excitatory effects can influence muscle activity.⁵⁵

Myofascial trigger points

Another motor effect of central excitation is the development of myofascial trigger points. Myofascial trigger points are characterized by localized areas of hypersensitive bands of muscle tissues found within the body of a muscle. The presence of these trigger points is paramount in the muscle pain condition called myofascial pain.^56,57,58 Continued deep pain input of significant intensity can induce the development of myofascial trigger points. The mechanism involved seems to be segmentally related to the site of primary pain. The masseter and temporalis are the masticatory muscles most frequently affected. The trigger point, in turn, refers pain that is frequently felt at or near the site of the initiating primary pain. The trigger itself, however, is usually silent unless manually palpated; then local muscle pain is felt. Although this mechanism may be initiated by pain, once trigger points become established, they remain active or latent until eliminated by therapeutic effort.^57,58 Thus, pain at or near the initial site of primary pain may persist as a continuing or recurrent heterotopic manifestation long after the original pain has ceased. The complexity of such pain problems makes accurate diagnosis all the more necessary for effective management of the patient’s complaint. Myofascial trigger point pain will be discussed in more detail in chapter 12.

The muscles that are affected by central sensitization are usually those innervated by the same major nerve that mediates deep pain input, thus establishing a segmental relationship. If the primary pain is mediated by the trigeminal nerve, the muscles most likely to be affected are those innervated by the trigeminal nerve. Eight muscles are innervated by the trigeminal nerve: the masseter, the temporalis, the medial pterygoid, the lateral pterygoid, the mylohyoid, the anterior belly of the digastric, and the tensor muscles of the soft palate and tympanic membrane.

Fig 4-6 Constant afferent nociceptive input can centrally excite efferent (motor) neurons, resulting in co-contraction of associated muscle or the development of myofascial trigger points.