Adaptive and Maladaptive Pain

Pain can be divided into two general categories recognized as adaptive and maladaptive. Adaptive pain protects the body from injury and promotes healing by inhibiting activity when injury has occurred. In contrast, maladaptive pain reflects pathologic activity of the nervous system—the result of complex processes of neuronal plasticity—pain as a disease state.5,6

Adaptive, everyday acute pain (Figure 14-1) is also known as nociceptive or physiologic pain and occurs when noxious stimuli (mechanical, thermal, or chemical) are transduced into electrical signals that are then transmitted to the spinal cord. These signals undergo modulation in the spinal cord before being relayed to the brain, where the conscious brain interprets these transmissions, resulting in pain perception. Adaptive pain is purposeful. Dr. Frank Vertosick states, “Pain is a teacher, the headmaster of nature’s survival school.”⁷ Acute pain tends to be of relatively short duration and, if addressed properly, is relatively easy to treat.

Chronic maladaptive pain may result from sustained noxious stimuli such as ongoing inflammation or profound tissue damage, or it may be present independent of the inciting cause. Regardless of its etiology, maladaptive pain offers no or little useful biologic function or survival advantage. The nervous system itself becomes the source of the pathology and contributes to patient morbidity. Effective treatment for maladaptive pain can be an enigma. A number of studies have shown that the longer a pain lingers, the harder it is to eradicate because of resultant changes to both the peripheral and central nervous system.

Chronic pain was traditionally defined as pain lasting more than 3 or 6 months, depending on the source of the definition.8,9 More recently, chronic pain has been defined as “pain that extends beyond the period of tissue healing and/or with low levels of identified pathology that are insufficient to explain the presence and/or extent of pain.”¹⁰ There is no general consensus on the definition of chronic pain. In clinical practice it is often difficult to determine when acute pain has become chronic—when adaptive pain crosses the threshold to become maladaptive.

Adaptive to Maladaptive Pain

A progression from adaptive to maladaptive pain can be described as a spectrum composed of three major stages or phases of pain, suggesting that different neurophysiologic mechanisms are involved, depending on the nature and time course of the originating stimulus.¹¹ These three phases are (1) the processing of a brief noxious stimulus, (2) the consequences of prolonged noxious stimulation, leading to tissue damage and peripheral inflammation, and (3) the consequences of neurologic damage or changes, including peripheral neuropathies and central pain states. This spectrum of architectural change within the nervous system and the resultant pain pathology may be represented graphically as in Figure 14-2.

The journey of the nervous system toward maladaptive pain is often described as windup. Windup describes activity-dependent plasticity characterized by a progressive increase in action potential output from dorsal horn neurons elicited during the course of prolonged, repeated low-frequency C-fiber or nociceptor stimuli.12,13 One receptor critical to this process is the N-methyl-D-aspartate (NMDA) receptor. NMDA receptors are only activated in the face of prolonged depolarization such as occurs with chronic pain.¹⁴ Their activation can cause neural cells to sprout new connective endings,¹⁵ thus expanding the receptive fields of the painful patient. Accompanying windup, less glutamate is required to transmit the pain signal and more antinociceptive input is required for analgesia. The complexity of maladaptive pain and the phenomenon of windup continues to provoke ongoing study. Studies have implicated activated microglia, norepinephrine (NE) levels, serotonin (5-HT) activity, as well as transient receptor potential (TRP) receptors as playing a role in maladaptive pain.

The rehabilitation practitioner must grasp the concept of this transition from adaptive to maladaptive pain in order to understand how best to address the pain management needs of the patient that is presented for physiotherapy. There are multiple potential targets of analgesic treatment in the patient experiencing both adaptive and maladaptive pain. It is appropriate, when putting together the pain management strategy for a specific patient, to address whatever targets of therapy may be relevant. The rehabilitation practitioner must work in tandem with the primary care practitioner, the surgeon (when appropriate), and the dog’s human companions to facilitate open and reciprocal communication about the patient’s pain status at every stage of treatment. Some patients require a very complex and aggressive pain management protocol to accomplish the goals of physical rehabilitation. As physiotherapy progresses, and the patient improves, the pain management strategy must be adjusted to meet those changing needs. Likewise, if the patient worsens during rehabilitation, reassessment of the patient and revision of its pain protocol are essential. Without some understanding of the complexities of long-standing pain, and of treating pain as a disease in and of itself, the rehabilitation patient may suffer needlessly.

Preemptive Analgesia

Pain memories imprinted within the CNS, mediated by NMDA receptors, produce hyperalgesia and contribute to allodynia—pain that is produced by a stimulus that does not normally provoke pain. A preoperative blockade of nociception may prevent postsurgical wound pain or pain hypersensitivity following surgery. This is the concept of preemptive analgesia articulated by the eminent pain physiologist Patrick Wall.¹⁶ In 1988, Professor Patrick Wall introduced the concept of preemptive analgesia to clinicians with his editorial in the journal Pain.¹⁷ Successful preemptive analgesia must meet three criteria. It must be (1) intense enough to block all nociception, (2) wide enough to cover the entire surgical area, and (3) prolonged enough to last throughout surgery and even into the postoperative period.

General anesthesia with an inhalant agent (e.g., isoflurane, sevoflurane) does not prevent central sensitization. The potential for central sensitization exists even in unconscious patients who are unresponsive to surgical stimuli.18,19 Noxious stimuli still enter the spinal cord during apparently adequate anesthesia.²⁰ The purpose of preemptive analgesia is to prevent sensitization of the nervous system throughout the perioperative period. Pain is to be expected from an initial surgery and the hypersensitivity that subsequently develops. Analgesia administered after sensitization may decrease pain somewhat, but has little long-term benefit in addressing the pain resulting from postsurgical inflammation. Analgesia administered before surgery limits inflammatory pain and decreases subsequent hypersensitivity. The most effective preemptive analgesic regimen occurs when it is initiated before surgery and continued throughout the postoperative period. Equally important is to use a complement of medications that work synergistically; for example, an opioid, alpha-2 agonist, NMDA antagonist, local anesthesia, and an NSAID.^21–23 It bears reminding that good nursing care in the immediate postoperative period can contribute to the comfort of the surgical patient.²⁴

Postoperative Analgesia

For the majority of rehabilitation patients that have experienced surgery, NSAIDs form the foundation of pain management in the postoperative period. Antiinflammatory drugs play such a substantial role in perioperative pain management²⁵ because surgery cannot be performed without subsequent inflammation. Reducing the inflammatory response in the periphery, and thereby decreasing sensitization of the peripheral nociceptors, should attenuate central sensitization.²⁶ In human medicine, the use of perioperative NSAIDs has reduced the use of patient-controlled analgesic morphine by 40% to 60%.^27,28

Depending upon the patient’s needs, an NSAID may be adequate as a stand-alone pain management agent. However, the rehabilitation practitioner must be especially vigilant about pain issues in the immediate postoperative period. Inadequately managed postoperative (adaptive) pain can transition to maladaptive pain, creating additional problems for the physiotherapy patient. A postoperative rehabilitation patient should be assessed for pain regularly, both at the time of therapy and through conversation and questioning with the pet owner to evaluate activities of daily living. One source of methods for scoring and evaluating pain may be found in the AAHA/AAFP Pain Management Guidelines for Dogs and Cats.²⁹ It may be that a postsurgical patient may need one or more of the adjunctive pain management strategies outlined in the following chronic pain section.

Nonsteroidal Antiinflammatory Drugs

Nonsteroidal antiinflammatory drugs remain the cornerstone for treating pain associated with degenerative joint disease (osteoarthritis; OA) and other sources of chronic pain. Nonsteroidal antiinflammatory drugs have effects at numerous locations along nociceptive pathways, both peripherally and centrally. This class of drugs manifests antiprostaglandin effects peripherally, but they are also considered central-acting because of their inhibition of cyclooxygenase within the dorsal horn of the spinal cord. Cyclooxygenase-2 (COX-2)–mediated PGE₂ production contributes to a late-onset, prolonged, and diffuse phase of central sensitization.³⁶ Cyclooxygenase-2-specific NSAIDs dampen central sensitization, and therefore play an important role in a multimodal pain management strategy. Cyclooxygenase-1–sparing NSAIDs (Deracoxib,³⁷ meloxicam, and firocoxib³⁸) have their optimal theoretical advantage where there is concern for platelet aggregation, or homeostasis.

The integration of an NSAID in a pain management protocol is particularly appealing when considering the theory by some³⁹ that the origin of all pain is inflammation and the inflammatory response. However, it must be appreciated that the ceiling effect of NSAIDs can limit their analgesic potential, thereby suggesting they are best, when used alone, for mild and moderate pain. Among a population of canine pain patients, all NSAIDs are effective, but a practitioner may witness variable responses to NSAIDs among individuals.